Efficacy and Safety of CAZ-AVI in the Treatment of Infections Due to Carbapenem-resistant G- Pathogens in Chinese Adults

AN OPEN-LABEL, RANDOMIZED, MULTI-CENTER, ACTIVE-CONTROLLED STUDY TO ESTIMATE THE EFFICACY AND SAFETY OF CEFTAZIDIME-AVIBACTAM (CAZ-AVI) VERSUS BEST AVAILABLE TREATMENT (BAT) IN THE TREATMENT OF INFECTIONS DUE TO CARBAPENEM-RESISTANT GRAM-NEGATIVE PATHOGENS IN CHINESE ADULTS

This is an open-label, randomized, multi-center, interventional, active-controlled Phase 4 study to evaluate the efficacy and safety of CAZ-AVI versus BAT in the treatment of infected participants with selected infection types (Hospital Acquired Pneumonia [HAP] (including Ventilator-Associated Pneumonia [VAP]); Complicated Urinary-Tract Infection [cUTI]; Complicated Intra-Abdominal Infection [cIAI]; Bloodstream Infection [BSI]) due to carbapenem-resistant Gram-negative pathogens in China.This study will be an estimation study. The statistical inference will be based on point estimate and confidence interval.

Study Overview

• Status: Completed
• Conditions: Bacteremia; Urinary Tract Infection; Intra-abdominal Infection; Hospital Acquired Pneumonia; Acute Pyelonephritis; Ventilator-associated Pneumonia
• Intervention / Treatment: Drug: Zavicefta, Ceftazidime-Avibactam; Drug: Best Available Treatment

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• China
  • Jiangyin, China, 214400
    • Jiangyin People's Hospital
  • Shanghai, China, 200240
    • Shanghai Fifth People's Hospital, Fudan University
  • Anhui
    • Bengbu, Anhui, China, 233004
      • The First affiliated hospital of bengbu medical college
    • Bengbu, Anhui, China, 233000
      • The First Affiliated Hospital of Bengbu Medical
    • Chizhou, Anhui, China, 247000
      • Chizhou People's Hospital
    • Fuyang, Anhui, China, 236000
      • Fuyang People's Hospital
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
  • Fujian
    • Xiamen, Fujian, China, 361004
      • Zhongshan Hospital Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
    • Qingyuan, Guangdong, China, 511518
      • Qingyuan People's Hospital
    • Shenzhen, Guangdong, China, 518020
      • ShenZhen People's Hospital
    • Shenzhen, Guangdong, China, 518035
      • The second people's Hospital of Shenzhen
    • Zhanjiang, Guangdong, China, 524000
      • Affiliated Hospital of Guangdong Medical University
  • Guangxi
    • Guilin, Guangxi, China, 541001
      • Affiliated Hospital of Guilin Medical College
  • Guizhou
    • Zunyi, Guizhou, China, 563000
      • Affiliated Hospital of Zunyi Medical University
  • Hebei
    • Baoding, Hebei, China, 071000
      • Affiliated Hospital of Hebei University
  • Henan
    • Luoyang, Henan, China, 471009
      • Luoyang Central Hospital
    • Nanyang, Henan, China, 473000
      • Nanyang Central Hospital
    • Zhengzhou, Henan, China, 450003
      • Henan Provincial People's Hospital
    • Zhengzhou, Henan, China, 450000
      • Henan Provincial People's Hospital
  • Inner Mongolia Autonomous Region
    • Baotou, Inner Mongolia Autonomous Region, China, 014000
      • Baotou Central Hospital
  • Jiangsu
    • Jiangyin, Jiangsu, China, 214400
      • Jiangyin People's Hospital
    • Xuzhou, Jiangsu, China, 221006
      • Affiliated Hospital of Xuzhou Medical University
    • Yangzhou, Jiangsu, China, 225001
      • Subei People's Hospital of Jiangsu province
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital, Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610055
      • Chengdu Xinhua Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300222
      • Tianjin Chest Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650034
      • The First people's Hospital of Kunming
    • Kunming, Yunnan, China, 650034
      • The First People's Hospital of Kunming (South Hospital)
    • Kunming, Yunnan, China, 650224
      • The First People's Hospital of Kunming Ganmei Hospital (North Hospital)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital
    • Hangzhou, Zhejiang, China, 310013
      • Zhejiang Hospital
    • Lishui, Zhejiang, China, 323000
      • Lishui People's Hospital
    • Taizhou, Zhejiang, China, 317000
      • Taizhou Hospital of Zhejiang Province
    • Wenzhou, Zhejiang, China, 325035
      • The 2nd Affiliated Hospital of WMU
    • Wenzhou, Zhejiang, China, 325099
      • Wenzhou Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female >18 years of age
• Participant must have a diagnosis of an infection (HAP/VAP, cUTI, cIAI, BSI) due to confirmed carbapenem-resistant aerobic Gram-negative pathogens, requiring administration of IV antibacterial therapy
• Participant who had received appropriate prior empiric antibacterial therapy for a carbapenem-resistant pathogen must meet at least 1 of the following criteria: no or no more than 24h; worsening of objective symptoms or signs after at least 48 hours of antibacterial therapy; no change of objective symptoms or signs after at least 72 hours of antibacterial therapy.
• Capable of giving signed informed consent

Exclusion Criteria:

• Other medical or psychiatric condition may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Participant is expected to require more than 21 days of treatment
• Participants who need more than 3 systemic antibiotics as part of best available treatment (BAT)
• Previous administration with an investigational drug within 30 days or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).
• Participant is pregnant or breastfeeding.
• Acute Physiology and Chronic Health Evaluation (APACHE) II score >30 or <10 using the most recent available data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAZ-AVI; ceftazidime 2g plus avibactam 0.5g	Drug: Zavicefta, Ceftazidime-Avibactam; CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as a 2 hour infusion every 8 hours. Dose adjustments are available for participants with CrCL ≤50 mL/min.
Active Comparator: Best Available Treatment; Based on investigative site practice and local epidemiology and guideline	Drug: Best Available Treatment; main treatment expected to be used as either monotherapy or in combination are colistin, tigecycline, fosfomycin, amikacin, and meropenem

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of participants in Microbiologically Modified Intent to Treat (mMITT) analysis set having clinical cure	Test of Cure (TOC, Day 21 - 25)

Secondary Outcome Measures

Outcome Measure	Time Frame
The percentage of participants in mMITT analysis set having clinical cure	End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose)
The percentage of participants in Microbiologically Evaluable (ME) analysis set having clinical cure	End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose)
The percentage of participants in ME analysis set having clinical cure	Test of Cure (TOC, Day 21-Day 25)
The percentage of participants in mMITT analysis set having favorable microbiological response	Test of Cure(TOC, Day 21-Day 25)
The percentage of participants in mMITT analysis set having favorable microbiological response	End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose)
The percentage of participants in ME analysis set having favorable microbiological response	End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose)
The percentage of participants in ME analysis set having favorable microbiological response	Test of Cure(TOC, Day 21-Day 25)
The percentage of participants who have died due to any cause	Day 28
The number of treatment-emergent adverse events	up to 32 days after the last dose of study intervention
The percentage of participants experiencing the AEs	up to 32 days after the last dose of study intervention

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2021
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Cross Infection; Iatrogenic Disease; Sepsis; Nephritis; Nephritis, Interstitial; Pyelitis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Communicable Diseases; Healthcare-Associated Pneumonia; Pneumonia; Intraabdominal Infections; Bacteremia; Urinary Tract Infections; Pneumonia, Ventilator-Associated; Pyelonephritis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Avibactam; Ceftazidime; Avibactam, ceftazidime drug combination
• Other Study ID Numbers: C3591033

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: No
• Studies a U.S. FDA-regulated device product: No