A Study to Determine the Efficacy, Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem (MER) ± Colistin (COL) for the Treatment of Serious Infections Due to Gram Negative Bacteria. (REVISIT)

November 19, 2024 updated by: Pfizer

A PHASE 3 PROSPECTIVE, RANDOMIZED, MULTICENTER, OPEN-LABEL, CENTRAL ASSESSOR-BLINDED, PARALLEL GROUP, COMPARATIVE STUDY TO DETERMINE THE EFFICACY, SAFETY AND TOLERABILITY OF AZTREONAM-AVIBACTAM (ATM-AVI) ±METRONIDAZOLE (MTZ) VERSUS MEROPENEM±COLISTIN (MER±COL) FOR THE TREATMENT OF SERIOUS INFECTIONS DUE TO GRAM NEGATIVE BACTERIA, INCLUDING METALLO-Β-LACTAMASE (MBL) - PRODUCING MULTIDRUG RESISTANT PATHOGENS, FOR WHICH THERE ARE LIMITED OR NO TREATMENT OPTIONS

A Phase 3 comparative study to determine the efficacy, safety and tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) versus Meropenem (MER) ± Colistin (COL) for the treatment of serious infections due to Gram negative bacteria.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A Phase 3 Prospective, Randomized, Multicenter, Open Label, Central Assessor Blinded, Parallel Group, Comparative Study To Determine The Efficacy, Safety And Tolerability Of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem±Colistin (MER±COL) For The Treatment Of Serious Infections Due To Gram Negative Bacteria, Including Metallo Β Lactamase (MBL) - Producing Multidrug Resistant Pathogens, For Which There Are Limited Or No Treatment Options

Study Type

Interventional

Enrollment (Actual)

422

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Argentina
- - Córdoba, Argentina, 5000
    - Hospital San Roque
- Santa FE
  - Rosario, Santa FE, Argentina, 2000
    - Sanatorio Británico
  - Santo Tome, Santa FE, Argentina, S3016
    - Sanatorio Servicios Medicos SM
Bulgaria
- - Sofia, Bulgaria, 1431
    - University Hospital Alexandrovska, Clinic of Anesthesiology and Intensive Care
  - Sofia, Bulgaria, 1527
    - University Hospital Queen Joanna ISUL, Clinic of Surgery
  - Stara Zagora, Bulgaria, 6003
    - University Multiprofile Hospital for Active Treatment ''Prof.Dr Stoyan Kirkovich''AD
China
- - Beijing, China, 100044
    - Peking University People's Hospital
  - Jiangyin, China, 214400
    - Jiangyin People'S Hospital
  - Tianjin, China, 300000
    - Tianjin Union Medical Center
- Beijing
  - Beijing, Beijing, China, 100191
    - Peking University Third Hospital
- Fujian
  - Zhangzhou, Fujian, China, 363000
    - Zhangzhou Municipal Hospital of Fujian Province
- Guangdong
  - Guangzhou, Guangdong, China, 510280
    - Zhujiang Hospital of Southern Medical University
  - Shantou, Guangdong, China, 515041
    - The First Affiliated Hospital of Shantou University Medical College
  - Shenzhen, Guangdong, China, 518035
    - The Second People's Hospital of Shenzhen
- Guangxi
  - Guilin, Guangxi, China, 541001
    - Affiliated Hospital of Guilin Medical University
- Guangxi Zhuang Autonomous Region
  - Nanning, Guangxi Zhuang Autonomous Region, China, 530022
    - Nanning First People's Hospital
- Hunan
  - Changsha, Hunan, China, 410005
    - Hunan Province People's Hospital
  - Changsha, Hunan, China, 410000
    - Changsha Third Hospital
- Inner Mongolia Autonomous Region
  - Baotou, Inner Mongolia Autonomous Region, China, 014000
    - Baotou Central Hospital
- Jiangsu
  - Jiangyin, Jiangsu, China, 214400
    - Jiangyin People'S Hospital
  - Zhenjiang, Jiangsu, China, 212001
    - Affiliated Hospital of Jiangsu University
- Shanghai
  - Shanghai, Shanghai, China, 200040
    - Huashan Hospital, Fudan University
  - Shanghai, Shanghai, China, 200433
    - Shanghai Pulmonary Hospital
- Yunnan
  - Kunming, Yunnan, China, 650034
    - The First People's Hospital of kunming
- Zhejiang
  - Hangzhou, Zhejiang, China, 310003
    - The First Affiliated Hospital of College of Medicine, Zhejiang University
  - Linhai, Zhejiang, China, 317000
    - Taizhou Hospital of Zhejiang Province
  - Lishui, Zhejiang, China, 323000
    - Lishui People's Hospital
  - Quzhou, Zhejiang, China, 324000
    - Quzhou people's Hospital
Croatia
- - Osijek, Croatia, 31000
    - University Hospital Centre Osijek
  - Slavonski Brod, Croatia, 35000
    - General Hospital "Dr. Josip Bencevic" Slavonski Brod
  - Zagreb, Croatia, 10000
    - Clinical Hospital Dubrava
- GRAD Zagreb
  - Zagreb, GRAD Zagreb, Croatia, 10000
    - Klinicka bolnica Merkur
- Primorsko-goranska Zupanija
  - Rijeka, Primorsko-goranska Zupanija, Croatia, 51000
    - Klinicki Bolnicki Centar Rijeka
Czechia
- - Brno, Czechia, 625 00
    - Fakultni nemocnice Brno
  - Decin, Czechia, 40599
    - Krajska zdravotni, a.s. - Nemocnice Decin, o.z.
  - Decin, Czechia, 40599
    - Lekarna Nemocnice Decin, Krajska zdravotni, a.s.- Nemocnice Decin, o.z.
  - Kolin III, Czechia, 280 02
    - Public Hospital Kolin, a.s.
  - Kyjov, Czechia, 697 01
    - Nemocnice Kyjov, prispevkova organizace
  - Praha 10, Czechia, 100 34
    - Fakultní nemocnice Královské Vinohrady
Greece
- - Athens, Greece, 11527
    - General Hospital of Athens "Laiko"
  - Athens, Greece, 12462
    - University General Hospital "Attikon"
  - Athens, Greece, 10676
    - General Hospital of Athens "Evangelismos"
  - Athens, Greece, 11527
    - General and Chest Diseases Hospital "Sotiria"
  - Heraklion, Crete, Greece, 71110
    - University General Hospital of Heraklion
  - Larissa, Greece, 41110
    - University General Hospital of Larissa
  - Larissa, Greece, 41221
    - Koutlimbaneio and Triantafylleio General Hospital of Larissa
India
- - Ludhiana, India, 141001
    - Dayanand Medical College and Hospital
  - Pune, India
    - Sahyadri Specialty Hospital
  - Pune, India, 411004
    - Sahyadri Clinical Research & Development Center
- Andhra Pradesh
  - Visakhapatnam, Andhra Pradesh, India, 530002
    - King George Hospital
- Karnataka
  - Bangalore, Karnataka, India, 560054
    - M S Ramaiah Medical College and Hospitals
  - Bangalore, Karnataka, India, 560002
    - Victoria Hospital, Bangalore Medical College And Research Institute
  - Manipal, Karnataka, India, 576104
    - Kasturba Medical College and Hospital
  - Mysuru, Karnataka, India, 570004
    - JSS Hospital
- Kerala
  - Kochi, Kerala, India, 682041
    - Amrita Institute Of Medical Sciences & Research Centre
  - Kozhikode, Kerala, India, 673008
    - Government Medical College, Kozhikode
- Maharashtra
  - Pune, Maharashtra, India, 411004
    - Sahyadri Super Specialty Hospital
  - Pune, Maharashtra, India, 411004
    - Sahyadri Super Speciality Hospital
  - Pune, Maharashtra, India, 411004
    - Deenanath Mangeshkar Hospital and Research Centre
- Rajasthan
  - Jaipur, Rajasthan, India, 302001
    - S.R. Kalla Memorial Gastro & General Hospital
- Tamil NADU
  - Chennai, Tamil NADU, India, 600006
    - Apollo Hospitals
- Uttar Pradesh
  - Lucknow, Uttar Pradesh, India, 226003
    - King George's Medical University
Israel
- - Ashdod, Israel, 7747629
    - Assuta Ashdod University Hospital
  - Haifa, Israel, 3109601
    - Rambam Health Care Campus
  - Jerusalem, Israel, 9112001
    - Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem
  - Petah Tikva, Israel, 4941492
    - Rabin Medical Center, Beilinson Hospital
  - Tel Aviv, Israel, 6423906
    - Tel Aviv Sourasky Medical Center
  - Tel-Hashomer, Israel, 5265601
    - The Chaim Sheba Medical Center
  - Zerifin, Israel, 7030000
    - Shamir Medical Center, Infectious Diseases Unit
Italy
- - Foggia, Italy, 71122
    - Azienda Ospedaliero-Universitaria Ospedali Riuniti
  - Modena, Italy, 41124
    - Azienda Ospedaliero Universitaria di Modena
  - Modena, Italy, 41124
    - Farmacia Ospedaliera - Direzione Assistenza Farmaceutica
  - Modena, Italy, 41124
    - SC di Radiologia - Azienda Ospedaliera Universitaria di Modena
  - Pisa, Italy, 56100
    - Azienda Ospedaliero-Universitaria Pisana Ospedale Cisanello
  - Pisa, Italy, 56100
    - UO Radiognastostica 2 Azienda Ospedaliero-Universitaria Pisana Ospedale Cisanello
  - Pisa, Italy, 56126
    - UO Farmaceutica Azienda Ospedaliero-Universitaria Pisana
  - Udine, Italy, 33100
    - Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Presidio Ospedaliero Universitario Santa
- Milan
  - Milano, Milan, Italy, 20122
    - Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Korea, Republic of
- - Seoul, Korea, Republic of, 03080
    - Seoul National University Hospital
  - Seoul, Korea, Republic of, 07441
    - Hallym University Kangnam Sacred Heart Hospital
  - Seoul, Korea, Republic of, 03312
    - The Catholic University of Korea, Eunpyeong St. Mary's Hospital
- Incheon Gwang'yeogsiv
  - Incheon, Incheon Gwang'yeogsiv, Korea, Republic of, 21565
    - Gachon University Gil Medical Center - Infectious Disease
Malaysia
- - Kuala Lumpur, Malaysia, 59100
    - University Malaya Medical Centre
- Pulau Pinang
  - Seberang Jaya, Pulau Pinang, Malaysia, 13700
    - Hospital Seberang Jaya
- Terengganu
  - Kuala Terengganu, Terengganu, Malaysia, 20400
    - Hospital Sultanah Nur Zahirah
Mexico
- Jalisco
  - Guadalajara, Jalisco, Mexico, 44280
    - Hospital Civil Fray Antonio Alcalde
- Nuevo LEON
  - Monterrey, Nuevo LEON, Mexico, 64460
    - Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
Philippines
- - Baguio City, Philippines, 2600
    - Baguio General Hospital and Medical Center
  - Davao City, Philippines, 8000
    - Davao Doctors Hospital
  - Iloilo City, Philippines, 5000
    - West Visayas State University Medical Center
  - Iloilo City, Philippines, 5000
    - St. Paul's Hospital of Iloilo, Inc.
  - Makati City, Philippines, 1229
    - Makati Medical Center
  - Manila, Philippines, 1000
    - Philippine General Hospital, Central Intensive Care Unit
  - Muntinlupa City, Philippines, 1780
    - Asian Hospital and Medical Center
  - Quezon City, Philippines, 1109
    - Quirino Memorial Medical Center
  - Quezon City, Philippines, 1112
    - St. Luke's Medical Center
- Cavite
  - City Of Dasmarinas, Cavite, Philippines, 4114
    - De La Salle Medical and Health Sciences Institute
Romania
- - Bucuresti, Romania, 021105
    - Institutul National De Boli Infectioase "Prof. Dr. Matei Bals"
  - Bucuresti, Romania, 030303
    - Spitalul Clinic de Boli Infecțioase și tropicale "Dr. Victor Babeș"
  - Cluj-Napoca, Romania, 400348
    - Spitalul Clinic de Boli Infectioase Cluj-Napoca
  - Iasi, Romania, 700116
    - Spitalul Clinic de Boli Infectioase "Sf. Parascheva" Iasi
  - Timisoara, Romania, 300723
    - Spitalul Clinic Judetean de Urgenta "Pius Brinzeu"
Russian Federation
- - Chelyabinsk, Russian Federation, 454048
    - Private Healthcare Institution "Clinical Hospital 'Russian Railroad Medicine, Chelyabinsk'"
  - Krasnodar, Russian Federation, 350012
    - State Budgetary Healthcare Institution "Regional Clinical Hospital No. 2" of the Ministry of Health
  - Novosibirsk, Russian Federation, 630051
    - GBUZ of Novosibirsk region "City Clinical Hospital # 2"
  - Perm, Russian Federation, 614107
    - State autonomous institution of healthcare of the Perm Region" City clinical hospital #4"
  - Saint-Petersburg, Russian Federation, 197022
    - FGBOU VO "The First St. Petersburg state medical university n. a. I.P. Pavlova"
  - Smolensk, Russian Federation, 214018
    - OGBUZ "Smolensk Regional Clinical Hospital"
  - Smolensk, Russian Federation, 214019
    - FSBEI of HE "Smolensk State Medical University" of the Ministry of Health of the RF
  - Smolensk, Russian Federation, 214019
    - Scientific Research Institute of Antimicrobial Chemotherapy
Spain
- - Barcelona, Spain, 08041
    - Hospital de la Santa Creu i Sant Pau
  - Barcelona, Spain, 08003
    - Parc de Salut Mar- Hospital del Mar
  - Cordoba, Spain, 14004
    - Hospital Universitario Reina Sofia
  - Madrid, Spain, 28034
    - Hospital Universitario Ramon y Cajal
  - Malaga, Spain, 29010
    - Hospital Regional Universitario de Málaga
  - Sevilla, Spain, 41009
    - Hospital Universitario Virgen Macarena
  - Sevilla, Spain, 41013
    - Hospital Universitario Virgen del Rocío
  - Valencia, Spain, 46026
    - Hospital Universitari i Politècnic La Fe
  - Zaragoza, Spain, 50009
    - Hospital Universitario Miguel Servet
- Barcelona
  - Badalona, Barcelona, Spain, 08916
    - Hospital Universitari Germans Trias i Pujol
  - Terrassa, Barcelona, Spain, 08221
    - Hospital Universitario Mutua de Terrassa
- Pontevedra
  - Vigo, Pontevedra, Spain, 36312
    - Complejo Hospitalario Universitario de Vigo. Area Sanitaria de Vigo. Hospital Alvaro Cunqueiro
Taiwan
- - Kaohsiung, Taiwan, 81362
    - Kaohsiung Veterans General Hospital
  - Kaohsiung City, Taiwan, 807
    - Kaohsiung Medical University Chung-Ho Memorial Hospital
  - Taichung City, Taiwan, 40705
    - Taichung Veterans General Hospital
  - Taipei, Taiwan, 116
    - Taipei Municipal Wanfang Hospital
  - Taipei City, Taiwan, 10002
    - National Taiwan University Hospital
- Yunlin
  - Douliou, Yunlin, Taiwan, 64041
    - National Taiwan University Hospital Yun-Lin Branch
Thailand
- Bangkok
  - Bangkoknoi, Bangkok, Thailand, 10700
    - Faculty of Medicine Siriraj Hospital
- Khon Kaen
  - Muang, Khon Kaen, Thailand, 40002
    - Srinagarind Hospital, Division of Infectious Disease and Tropical Medicine
- Nonthaburi
  - Muang, Nonthaburi, Thailand, 11000
    - Bamrasnaradura Infectious Disease Institute (BIDI)
- Songkhla
  - Hat Yai, Songkhla, Thailand, 90110
    - Songklanagarind Hospital, Prince of Songkla University
Turkey
- - Ankara, Turkey, 06100
    - Hacettepe Universitesi Tip Fakultesi
  - Ankara, Turkey, 06230
    - Ankara University Faculty of Medicine
  - Ankara, Turkey, 06800
    - T.C. Saglik Bakanligi Ankara Sehir Hastanesi
  - Istanbul, Turkey, 34899
    - Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi
  - Istanbul, Turkey, 34303
    - Acibadem Atakent Hospital
  - Izmir, Turkey, 35040
    - Ege University Faculty of Medicine
  - Kocaeli, Turkey, 41380
    - Kocaeli University Medical Faculty
  - Trabzon, Turkey, 61080
    - Karadeniz Technical University Medical Faculty Farabi Hospital
Ukraine
- - Chernivtsi, Ukraine, 58001
    - OKU "Chernivetska oblasna klinichna likarnia", khirurhichne viddilennia
  - Dnipro, Ukraine, 49005
    - KZ "Dnipropetrovska oblasna klinichna likarnia im. I.I. Mechnykova", viddilennia khirurhii №2
  - Dnipro, Ukraine, 49102
    - Komunalnyi zaklad "Miska klinichna likarnia No.4" Dniprovskoi miskoi rady, viddilennia profpatolohii
  - Ivano-Frankivsk, Ukraine, 76008
    - Oblasna klinichna likarnia, viddilennia anesteziolohii ta intensyvnoi terapii
  - Ivano-Frankivsk, Ukraine, 76018
    - Ivano-Frankivska tsentralna miska klin likarnia, viddilennia khirurhii,
  - Kharkiv, Ukraine, 61103
    - DU "Instytut zahalnoi ta nevidkladnoi khirurhii imeni V.T. Zaitseva Natsionalnoi akademii medychnykh
  - Kyiv, Ukraine, 02125
    - Kyivska miska klinichna likarnia No. 3, khirurhichne viddilennia
  - Kyiv, Ukraine, 03110
    - Kyivska miska klinichna likarnia #4, khirurhichne viddilennia #1
  - Lviv, Ukraine, 79010
    - Komunalne nekomertsiine pidpryiemstvo Lvivskoi oblasnoi rady Lvivska oblasna klinichna likarnia
  - Odesa, Ukraine, 65059
    - Odeska klinichna likarnia na zaliznychnomu transporti filii "Tsentr okhorony zdorovia" aktsionernoho
  - Poltava, Ukraine, 36039
    - Komunalne pidpryiemstvo "1-a miska klinichna likarnia Poltavskoi miskoi rady",
  - Vinnytsia, Ukraine, 21018
    - Vinnytska oblasna klinichna likarnia im. M.I. Pyrohova
United States
- Arizona
  - Tucson, Arizona, United States, 85719
    - Banner University Medical Center - Tucson
- California
  - Torrance, California, United States, 90502
    - Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  - Torrance, California, United States, 90509
    - Harbor-UCLA Medical Center
- Illinois
  - Springfield, Illinois, United States, 62781
    - Memorial Medical Center
  - Springfield, Illinois, United States, 62702
    - Southern Illinois University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Description

Inclusion Criteria:

All subjects:

Male or female from 18 years of age
Provision of informed consent
Confirmed diagnosis of HAP/VAP or cIAI requiring iv antibiotic treatment
Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met and negative pregnancy test

Additional for cIAI:

Diagnosis of cIAI, EITHER:
Intra-operative/postoperative enrolment with visual confirmation of cIAI. OR Preoperative enrollment with evidence of systemic inflammatory response, physical and radiological findings consistent with cIAI; confirmation of cIAI at time of surgery within 24 hours of study entry
Surgical intervention within 24 hours (before or after) the administration of the first dose of study drug

Additional for HAP/VAP:

Onset symptoms > 48h after admission to or <7 days after discharge from an inpatient care facility
New or worsening infiltrate on CXR or CT scan
Clinical signs and symptoms and laboratory findings consistent with HAP/VAP
Respiratory specimen obtained for Gram stain and culture following onset of symptoms and prior to randomisation

Exclusion criteria:

All subjects:

APACHE II score > 30
Confirmed or suspected infection caused by Gram-negative species not expected to respond to study drug, or Gram-positive species
Receipt of >24 hr systemic antibiotic within 48h prior to randomisation (exception in case of treatment failure)
History of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem,monobactam or other β-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the study drugs
Known Clostridium difficle associated diarrhoea
Requirement for effective concomitant systemic antibacterials or antifungals
Creatinine clearance ≤15 ml/min or requirement or expectation for renal replacement therapy
Acute hepatitis, cirrhosis, acute hepatic failure, chronic hepatic failure
Hepatic disease as indicated by AST or ALT >3 × ULN. Patients with AST and/or ALT up to 5 × ULN are eligible if acute and documented by the investigator as being directly related infectious process
Patient has a total bilirubin >2 × ULN, unless isolated hyperbilirubinemia is directly related to infectious process or due to known Gilbert's disease
ALP >3 × ULN. Patients with values >3 × ULN and <5 x ULN are eligible if acute and directly related to the infectious process being treated
Absolute neutrophil count <500/mm3
Pregnant or breastfeeding or if of child bearing potential, not using a medically accepted effective method of birth control.
Any other condition that may confound the results of the study or pose additional risks to the subject
Unlikely to comply with protocol
History of epilepsy or seizure disorders excluding febrile seizures of childhood

Additional for cIAI

Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours of diagnosis; perforation of gastroduodenal ulcer with surgery < 24 hours of diagnosis primary etiology is not likely to be infectious
Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess
Prior liver, pancreas or small-bowel transplant
Staged abdominal repair (STAR), open abdomen technique or marsupialisation

Additional for HAP/VAP

APACHE II score < 10
Known or high likelihood of Gram-positive monomicrobial infection
Lung abscess, pleural empyema, post-obstructive pneumonia
Lung or heart transplant
Myasthenia gravis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Single

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aztreonam-Avibactam ± Metronidazole All patients randomised to this arm will receive ATM-AVI; all patients with cIAI will receive MTZ for anaerobic cover	Drug: ATM-AVI (Creatinine clearance > 50 mL/min) 6500 mg ATM/2167 mg (loading dose, extended loading dose and maintenance dose) by iv infusion on Day 1 followed by a total daily dose of 6000 mg ATM/2000 mg AVI (Creatinine clearance 31 - 50 mL/min) 4250 mg ATM/1417 mg AVI on Day 1 (loading dose, extended loading dose, maintenance dose) followed by total daily dose 3000 mg ATM/1000 mg AVI (Creatinine clearance 16 - 30 mL/min) 2700 mg ATM/900 mg AVI on Day 1 (loading dose, extended loading dose maintenance dose), followed by total daily dose 2025 mg ATM/675 mg AVI Drug: MTZ For cIAI only; 500 mg/100 mL metronidazole iv infusion over 1hr q8h
Active Comparator: Meropenem ± Colistin All patients randomised to this arm will receive MER; addition of COL will be at investigator's discretion in line with local practice	Drug: MER Where pathogen initially not suspected of being MER-resistant: (Creatinine clearance > 50 mL/min) 1000 mg meropenem by 30 min iv infusion q8h (Creatinine clearance 26 - 50 mL/min) 1000mg meropenem by 30 min iv infusion q12h (Creatinine clearance 16 - 25 mL/min) 500 mg meropenem by 30 min iv infusion q12h Where pathogen initially suspected of being MER-resistant (Creatinine clearance > 50 mL/min) 2000 mg meropenem by 180 min iv infusion q8h (Creatinine clearance 26 - 50 mL/min) 2000 mg meropenem by 180 min iv infusion q12h (Creatinine clearance 16 - 25 mL/min) 1000 mg meropenem by 180 min iv infusion q12h Drug: COL Loading dose 9 million IU by 30 -60 min iv infusion (6 million IU where weight < 60 kg) followed by one of the following maintenance doses: (Creatinine clearance > 50 mL/min) after a 12h interval, commence maintenance dosing 9 million IU daily in 2 or 3 divided doses by 30 -60 min iv infusions. (Creatinine clearance 31 - 50 mL/min) After a 24 hr interval, commence maintenance dosing of 6 million IU daily in 2 divided doses by 30 -60 min iv infusion (Creatinine clearance 21 - 30 mL/min) After a 24 hr interval, commence maintenance dosing 5 million IU daily in 2 divided doses by 30 -60 min iv infusion (Creatinine clearance 16 - 20 mL/min) after a 24 hr interval, commence maintenance dosing 4 million IU daily in 2 divided doses by 30 -60 min iv infusion

Participant Group / Arm

Intervention / Treatment

Experimental: Aztreonam-Avibactam ± Metronidazole

All patients randomised to this arm will receive ATM-AVI; all patients with cIAI will receive MTZ for anaerobic cover

Drug: ATM-AVI

(Creatinine clearance > 50 mL/min) 6500 mg ATM/2167 mg (loading dose, extended loading dose and maintenance dose) by iv infusion on Day 1 followed by a total daily dose of 6000 mg ATM/2000 mg AVI

(Creatinine clearance 31 - 50 mL/min) 4250 mg ATM/1417 mg AVI on Day 1 (loading dose, extended loading dose, maintenance dose) followed by total daily dose 3000 mg ATM/1000 mg AVI

(Creatinine clearance 16 - 30 mL/min) 2700 mg ATM/900 mg AVI on Day 1 (loading dose, extended loading dose maintenance dose), followed by total daily dose 2025 mg ATM/675 mg AVI

Drug: MTZ

For cIAI only; 500 mg/100 mL metronidazole iv infusion over 1hr q8h

Active Comparator: Meropenem ± Colistin

All patients randomised to this arm will receive MER; addition of COL will be at investigator's discretion in line with local practice

Drug: MER

Where pathogen initially not suspected of being MER-resistant:

(Creatinine clearance > 50 mL/min) 1000 mg meropenem by 30 min iv infusion q8h

(Creatinine clearance 26 - 50 mL/min) 1000mg meropenem by 30 min iv infusion q12h

(Creatinine clearance 16 - 25 mL/min) 500 mg meropenem by 30 min iv infusion q12h

Where pathogen initially suspected of being MER-resistant (Creatinine clearance > 50 mL/min) 2000 mg meropenem by 180 min iv infusion q8h

(Creatinine clearance 26 - 50 mL/min) 2000 mg meropenem by 180 min iv infusion q12h

(Creatinine clearance 16 - 25 mL/min) 1000 mg meropenem by 180 min iv infusion q12h

Drug: COL

Loading dose 9 million IU by 30 -60 min iv infusion (6 million IU where weight < 60 kg) followed by one of the following maintenance doses:

(Creatinine clearance > 50 mL/min) after a 12h interval, commence maintenance dosing 9 million IU daily in 2 or 3 divided doses by 30 -60 min iv infusions.

(Creatinine clearance 31 - 50 mL/min) After a 24 hr interval, commence maintenance dosing of 6 million IU daily in 2 divided doses by 30 -60 min iv infusion

(Creatinine clearance 21 - 30 mL/min) After a 24 hr interval, commence maintenance dosing 5 million IU daily in 2 divided doses by 30 -60 min iv infusion

(Creatinine clearance 16 - 20 mL/min) after a 24 hr interval, commence maintenance dosing 4 million IU daily in 2 divided doses by 30 -60 min iv infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Cure at Test of Cure (TOC) Visit: Intent-To-Treat (ITT) Analysis Set Time Frame: At TOC visit (Day 28)	Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% confidence interval (CI) was based on Jeffrey's method.	At TOC visit (Day 28)
Percentage of Participants With Clinical Cure at TOC Visit: Clinically Evaluable (CE) Analysis Set Time Frame: At TOC visit (Day 28)	Clinical cure = improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. CE analysis set:all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens.	At TOC visit (Day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Cure at TOC Visit: Microbiological Intent-To-Treat (Micro-ITT) Analysis Set Time Frame: At TOC visit (Day 28)	Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method.	At TOC visit (Day 28)
Percentage of Participants With Clinical Cure at TOC Visit: Microbiologically Evaluable (ME) Analysis Set Time Frame: At TOC visit (Day 28)	Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method.	At TOC visit (Day 28)
Percentage of Participants With Clinical Cure at TOC Visit by Type of Infection: ITT Analysis Set Time Frame: At TOC visit (Day 28)	Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method.	At TOC visit (Day 28)
Percentage of Participants With Clinical Cure at TOC Visit by Type of Infection: CE Analysis Set Time Frame: At TOC visit (Day 28)	Clinical cure = improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee. 95% CI was based on Jeffrey's method. CE analysis set:all participants in ITT analysis set; met criteria for cIAI, or HAP/VAP; received at least 48 hours of study treatment or <48 hours of treatment before discontinuing study drug due to AE; no concomitant antibiotics for any baseline pathogens between first dose and TOC (except protocol-allowed antibiotics); no prior antibiotics other than allowed per protocol; no important protocol deviations; no clinical outcome of indeterminate at TOC; no monomicrobial infections due to non-eligible pathogens and did not have only Gram-positive pathogens.	At TOC visit (Day 28)
Percentage of Participants With Clinical Cure in Participants With Metallo-beta-lactamase (MBL) Positive Pathogen at TOC Visit: Micro-ITT Analysis Set Time Frame: At TOC visit (Day 28)	Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. Additionally, for cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee.	At TOC visit (Day 28)
Percentage of Participants With Clinical Cure in Participants With MBL Positive Pathogen at TOC Visit: ME Analysis Set Time Frame: At TOC visit (Day 28)	Clinical cure was defined as improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Clinical cure was determined by the Independent Clinical Adjudication Committee.	At TOC visit (Day 28)
Percentage of Participants With Favorable Per-Participant Microbiological Response at TOC Visit: Micro- ITT Analysis Set Time Frame: At TOC visit day (28)	Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure.	At TOC visit day (28)
Percentage of Participants With Favorable Per-Participant Microbiological Response at TOC Visit: ME Analysis Set Time Frame: At TOC Visit (Day 28)	Participants were determined to have a favorable microbiological response if all baseline pathogens for that participant had a favorable outcome (eradicated or presumed eradicated). Eradication: Absence of causative pathogen from an appropriately obtained specimen at the site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure.	At TOC Visit (Day 28)
Percentage of Participants Who Died on or Before 28 Days After Randomization: ITT Analysis Set Time Frame: From randomization up to 28 days	Percentage of participants who died on or before 28 days after randomization is reported in this outcome measure.	From randomization up to 28 days
Percentage of Participants Who Died on or Before 28 Days After Randomization: Micro-ITT Analysis Set Time Frame: From randomization up to 28 days	Percentage of participants who died on or before 28 days after randomization is reported in this outcome measure.	From randomization up to 28 days
Plasma Concentration of Aztreonam Time Frame: Anytime between 25 to 30 minutes, 3.25 to 3.5 hours, 5.5 to 6.5 hours, 7.5 to 8.5 hours post start of infusion on Day 1; 2.75 to 3 hours, 3.5 to 4.5 hours, 5 to 6 and 7 to 8 hours post start of infusion on Day 4	Plasma concentration for aztreonam according to renal function (augmented, normal and mild, moderate and severe is presented in this outcome measure. Augmented = Creatinine clearance (CrCL) > 150 milliliters per minute (mL/min); Normal & Mild = CrCL > 50 to <=150 mL/min; Moderate = CrCL > 30 to ≤ 50 mL/min; Severe = CrCL > 15 to ≤ 30 mL/min.	Anytime between 25 to 30 minutes, 3.25 to 3.5 hours, 5.5 to 6.5 hours, 7.5 to 8.5 hours post start of infusion on Day 1; 2.75 to 3 hours, 3.5 to 4.5 hours, 5 to 6 and 7 to 8 hours post start of infusion on Day 4
Plasma Concentration of Avibactam Time Frame: Anytime between 25 to 30 minutes, 3.25 to 3.5 hours, 5.5 to 6.5 hours, 7.5 to 8.5 hours post start of infusion on Day 1; 2.75 to 3 hours, 3.5 to 4.5 hours, 5 to 6 and 7 to 8 hours post start of infusion on Day 4	Plasma concentration for avibactam according to renal function (augmented, normal and mild, moderate and severe is presented in this outcome measure. Augmented = CrCL > 150 mL/min; Normal & Mild = CrCL > 50 to <=150 mL/min; Moderate = CrCL > 30 to ≤ 50 mL/min; Severe = CrCL > 15 to ≤ 30 mL/min.	Anytime between 25 to 30 minutes, 3.25 to 3.5 hours, 5.5 to 6.5 hours, 7.5 to 8.5 hours post start of infusion on Day 1; 2.75 to 3 hours, 3.5 to 4.5 hours, 5 to 6 and 7 to 8 hours post start of infusion on Day 4
Maximum Plasma Concentration for a Dosing Interval at Steady-State (Cmax, ss) According to Clinical Response by Infection Type at TOC: Aztreonam Time Frame: At TOC (Day 28)	Population PK predicted maximum plasma concentration for a dosing interval at steady-state (Cmax,ss) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	At TOC (Day 28)
Percentage of Time That Free Plasma Concentrations Are Above the Minimum Inhibitory Concentration Over a Dosing Interval (%fT>MIC Aztreonam (ATM) of 8 mg/L) According to Clinical Response by Infection Type at TOC: Aztreonam Time Frame: At TOC (Day 28)	Population PK predicted (%fT>MIC ATM of 8 mg/L) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	At TOC (Day 28)
Area Under the Plasma Concentration-time Curve Over 24 Hours at Steady-state (AUC24,ss ) According to Clinical Response by Infection Type at TOC: Aztreonam Time Frame: 0 to 24 hours at TOC (Day 28)	Population PK predicted (AUC24,ss) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	0 to 24 hours at TOC (Day 28)
Maximum Plasma Concentration for a Dosing Interval at Steady-state (Cmax,ss) According to Microbiological Response by Infection Type at TOC: Aztreonam Time Frame: At TOC (Day 28)	Population PK predicted (Cmax,ss) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving < 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	At TOC (Day 28)
Area Under the Plasma Concentration-time Curve Over 24 Hours at Steady-state (AUC24,ss) According to Microbiological Response by Infection Type at TOC: Aztreonam Time Frame: 0 to 24 hours at TOC (Day 28)	Population PK predicted (AUC24,ss) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving < 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	0 to 24 hours at TOC (Day 28)
Percentage of Time That Free Plasma Concentrations Are Above the Minimum Inhibitory Concentration Over a Dosing Interval (%fT>MIC Aztreonam (ATM) of 8 mg/L) According to Microbiological Response by Infection Type at TOC: Aztreonam Time Frame: At TOC (Day 28)	Population PK predicted (%fT>MIC ATM of 8 mg/L) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving < 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	At TOC (Day 28)
Area Under the Plasma Concentration-time Curve Over 24 Hours at Steady-state (AUC24,ss) According to Clinical Response by Infection Type at TOC: Avibactam Time Frame: 0 to 24 hours at TOC (Day 28)	Population PK predicted (AUC24,ss) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	0 to 24 hours at TOC (Day 28)
Maximum Plasma Concentration for a Dosing Interval at Steady-state (Cmax,ss ) According to Clinical Response by Infection Type at TOC: Avibactam Time Frame: At TOC (Day 28)	Population PK predicted (Cmax,ss) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	At TOC (Day 28)
Percent of Time That Free Plasma Concentrations Are Above the Threshold Concentration Over a Dosing Interval (%fT>CT of 2.5mg/L) According to Clinical Response by Infection Type at TOC: Avibactam Time Frame: At TOC (Day 28)	Population PK predicted (%fT>CT of 2.5mg/L) for participants who received aztreonam-avibactam in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Clinical response categories included, clinical cure=improvement in baseline signs and symptoms such that after study treatment, no further antimicrobial treatment for the index infection (i.e., cIAI or HAP/VAP) was required. For cIAI participants, no unplanned drainage or surgical intervention was necessary since the initial procedure. Failure was defined as participants who met any of the following criteria like death (after receiving at least 48 hours of study treatment) and participants who received treatment with further antibiotics for the index infection. Indeterminate was defined as death (after receiving less than 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	At TOC (Day 28)
Area Under the Plasma Concentration-time Curve Over 24 Hours at Steady-state (AUC24,ss) According to Microbiological Response by Infection Type at TOC: Avibactam Time Frame: 0 to 24 hours At TOC (Day 28)	Population PK predicted (AUC24,ss) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving<48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	0 to 24 hours At TOC (Day 28)
Maximum Plasma Concentration for a Dosing Interval at Steady-state (Cmax,ss (mg/L)) According to Microbiological Response by Infection Type at TOC: Avibactam Time Frame: At TOC (Day 28)	Population PK predicted (Cmax,ss (mg/L)) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving<48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	At TOC (Day 28)
Percent of Time That Free Plasma Concentrations Are Above the Threshold Concentration Over a Dosing Interval; (%fT>CT of 2.5 mg/L) According to Microbiological Response by Infection Type at TOC: Avibactam Time Frame: At TOC (Day 28)	Population PK predicted (%fT>CT of 2.5 mg/L) for participants who received ATM-AVI in studies C3601002 (NCT03329092) and C3601009 (NCT03580044). Microbiological response included Favorable =baseline pathogens for participant had a favorable outcome. Eradication: Absence of causative pathogen from an appropriately obtained specimen at site of infection. Presumed eradication: repeat culture of specimens were not performed/clinically indicated in a participant who had a clinical response of cure. Unfavorable=persistence, persistence with increasing MIC, or presumed persistence. Persistence= Causative organism still present from appropriately obtained specimen at site of infection. Presumed persistence= Participant assessed as a clinical failure and repeat culture of specimens were not performed/clinically indicated. Indeterminate = death (after receiving < 48 hours of study treatment) and for cIAI participants inadequate infection source control at time of initial surgical procedure.	At TOC (Day 28)
Number of Participants With Adverse Events (AEs) and Serious AEs Time Frame: From start of study treatment until end of late follow-up (Up to Day 45)	An adverse event (AE) was any untoward medical occurrence in a study participant administered medicinal product,; the event need not necessarily have a causal relationship with product treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital abnormal/birth defect or considered an important medical event.	From start of study treatment until end of late follow-up (Up to Day 45)
Number of Participants With Potentially Clinically Significant Hematology Abnormalities Time Frame: From start of study treatment until TOC visit (Up to Day 28)	Criteria for potential clinically significant hematology results were as follows: hemoglobin, hematocrit and erythrocyte <0.7lower limit of normal [LLN] and >30% decrease from Baseline (DFB); >1.3upper limit of normal (ULN) and >30% increase from Baseline (IFB). Platelet count <0.65LLN and > 50% decrease from baseline; > 1.5 ULN and > 100% increase from baseline. leukocyte: < 0.65* LLN and > 60% decrease from baseline; > 1.5* ULN and 100% increase from baseline. Neutrophils/leukocytes < 0.65 * LLN and >75% decrease from baseline; > 1.6ULN and > 100% increase from baseline. Lymphocytes/leukocytes < 0.25 LLN and > 75% decrease from baseline;> 1.5* ULN and > 100% increase from baseline, Eosinophils/leukocytes, Monocytes/leukocytes, Basophils/leukocytes > 4.0* ULN and > 300% increase from baseline.	From start of study treatment until TOC visit (Up to Day 28)
Number of Participants With Potentially Clinically Significant Clinical Chemistry Abnormalities Time Frame: From start of study treatment until At TOC visit (Up to Day 28)	Albumin < 0.5* LLN and> 50% decrease from baseline (DFB);> 1.5 * ULN and> 50% increase from baseline (IFB). Alkaline phosphatase < 0.5 * LLN and> 80% DFB;> 3.0 * ULN and> 100%. Alanine and Aspartate aminotransferase > 3.0 * ULN and> 100% IFB. Bicarbonate < 0.7 * LLN and > 40% DFB;> 1.3 * ULN and> 40% IFB. Blood urea nitrogen < 0.2 * LLN and > 100% DFB; > 3.0 * ULN and > 200% IFB. Calcium < 0.7 * LLN and > 30% DFB;> 1.3 * ULN and> 30% IFB. Chloride < 0.8 * LLN >and 20% DFB; > 1.2 * ULN and > 20% IFB. Creatinine > 2.0 * ULN and> 100% IFB; Glucose < 0.6 * LLN and> 40% DFB; > 3.0 * ULN and> 200% IFB. Potassium < 0.8 * LLN and > 20% DFB; > 1.2 * ULN and> 20% IFB. Sodium < 0.85 * LLN and> 10% DFB;> 1.1 * ULN and >10% IFB. Bilirubin > 1.5 * ULN and > 100% IFB.; Direct bilirubin > 2.0 * ULN and > 150% IFB.	From start of study treatment until At TOC visit (Up to Day 28)
Number of Participants With Abnormalities in Vital Signs Time Frame: From start of study treatment until TOC visit (Up to Day 28)	Vitals signs, included blood pressure and, heart rate. Blood pressure (BP) and heart rate were measured using a semiautomatic BP recording device with the participant in a supine position after at least 10 minutes of rest. Criteria for abnormalities included: Systolic BP (millimeters of mercury [mmHg]): value more than (>) 150 and increase from baseline more than equal (>= 30) or value less than (<) 90 and decrease from baseline >= 30; DBP: value > 100 and increase from baseline >=20 or Value < 50 and decrease from baseline >= 20; Heart Rate (beats per minute [BPM]): value < 40 or > 120.	From start of study treatment until TOC visit (Up to Day 28)
Number of Participants With Abnormal Physical Examination Finding Time Frame: Screening, End of treatment (up to 24 hours post infusion on Day 14) and Test of Cure (Day 28)	A complete physical examination was performed and included an assessment of the following: general appearance including site of infection, skin, head and throat (head, eyes, ears, nose, and throat), lymph nodes, lungs, cardiovascular (CV), abdomen, musculoskeletal, and neurological systems.	Screening, End of treatment (up to 24 hours post infusion on Day 14) and Test of Cure (Day 28)
Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Time Frame: Baseline (latest non-missing value before start of treatment) and Day 3	Standard 12-lead ECGs were recorded with the participants in the supine position after the participant had rested in this position for 10 minutes. Clinically significant findings were based on investigators assessment.	Baseline (latest non-missing value before start of treatment) and Day 3

Other Outcome Measures

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Collaborators

Biomedical Advanced Research and Development Authority

Innovative Medicines Initiative (IMI) COMBACTE-CARE (EU)

Investigators

Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

To obtain contact information for a study center near you, click here.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 5, 2018

Primary Completion (Actual)

February 23, 2023

Study Completion (Actual)

February 23, 2023

Study Registration Dates

First Submitted

October 6, 2017

First Submitted That Met QC Criteria

October 27, 2017

First Posted (Actual)

November 1, 2017

Study Record Updates

Last Update Posted (Actual)

December 10, 2024

Last Update Submitted That Met QC Criteria

November 19, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

C3601002
D4910C00004 (Other Identifier: Alias Study Number)
2017-002742-68 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Innovative Medicines Initiative (IMI) COMBACTE-CARE

Completed

Determine the PK and Safety and Tolerability of ATM-AVI for the Treatment of cIAIs in Hospitalized Adults (REJUVENATE)

Complicated Intra-Abdominal Infections, cIAIs

Spain, France, Germany
Pfizer
Allergan

Terminated

Efficacy, Safety, and Tolerability of ATM-AVI in the Treatment of Serious Infection Due to MBL-producing Gram-negative Bacteria

Serious Bacterial Infection

Romania, Taiwan, China, Malaysia, Thailand, Philippines, Argentina, Greece, India, United States, Mexico, Russian Federation
Sarepta Therapeutics, Inc.

Terminated

Safety and Efficacy Study of AVI-5126 When Used on Vein Grafts Before Use in Heart by-Pass Graft Surgery (CABG)

Cardiovascular Disease | Coronary Artery Bypass

Ukraine
Imperial College London
Sarepta Therapeutics, Inc.; Department of Health, United Kingdom

Completed

Safety and Efficacy Study of Antisense Oligonucleotides in Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy

United Kingdom
Sarepta Therapeutics, Inc.
United States Department of Defense

Completed

Safety Study of Single Administration Post-exposure Prophylaxis Treatment for Marburg Virus

Marburg Hemorrhagic Fever

United States
Chinese University of Hong Kong

Not yet recruiting

Augmented Velocity Index of Intra-abdominal, Carotid and Retinal Arteries

Arterial Stiffness
Sarepta Therapeutics, Inc.
United States Department of Defense

Completed

Safety Study of Single Administration Post-Exposure Prophylaxis Treatment for Ebola Virus

Ebola Hemorrhagic Fever

United States
Sarepta Therapeutics, Inc.

Terminated

An Exploratory Study of AVI-4020 in Patients With Possible Acute Neuroinvasive West Nile Virus (WNV) Disease

West Nile Fever

A Study to Determine the Efficacy, Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem (MER) ± Colistin (COL) for the Treatment of Serious Infections Due to Gram Negative Bacteria. (REVISIT)

Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Actual)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Other Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Collaborators

Investigators

Publications and helpful links

Helpful Links

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Actual)

Study Completion (Actual)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Actual)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

IPD Plan Description

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ukraine

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations