Safety and Efficacy Study to Compare IV CXA 101/Tazobactam and Metronidazole With Meropenem in Complicated Intraabdominal Infections

September 27, 2018 updated by: Cubist Pharmaceuticals LLC

A Multicenter, Double-Blind, Randomized, Phase 2 Study to Compare the Safety and Efficacy of Intravenous CXA 101/ Tazobactam and Metronidazole With That of Meropenem in Complicated Intraabdominal Infections

A Phase 2, multicenter, prospective, randomized, double-blind study of CXA-101/ tazobactam (1000/500 mg q8h) and metronidazole (500 mg q8h) IV infusion vs. meropenem IV infusion (1000 mg q8h) and a matching saline placebo (q8h) in the treatment of cIAI in adult subjects. Dose adjustments for subjects with mild renal impairment are not necessary and subjects with more severe degrees of renal failure are excluded.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
122

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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
      • C.a.b.a., Argentina, C1180AAX
        • Sanatorio Güemes
      • Cordoba, Argentina, X5000JRD
        • Hospital Nuestra Señora de la Misericordia
      • Cordoba, Argentina, X5000
        • Hospital San Roque
      • Mendoza, Argentina, M5500CHQ
        • Hospital Central de Mendoza
      • Santa Fe, Argentina, S3000EOZ
        • Hospital Dr. Jose Maria Cullen
    • Entre Ríos
      • Paraná, Entre Ríos, Argentina, E3100BBJ
        • Hospital San Martin
  • Georgia
      • Tbilisi, Georgia, 0102
        • Ltd Ivane Javakhishvili Tbilisi State University Center
      • Tbilisi, Georgia, 0159
        • JSC K.Eristavi National Center of Experimental and Clinical Surgery
      • Tbilisi, Georgia, 0160
        • Ltd Vakhtang Bochorishvili Antiseptic Center
      • Tbilisi, Georgia, 0160
        • Tbilisi State Hospital #4
  • Russian Federation
      • Moscow, Russian Federation, 105203
        • Federal State Institution
      • Moscow, Russian Federation, 109240
        • State Moscow Healthcare
      • Moscow, Russian Federation, 111020
        • State Healthcare Institution
      • Novosibirsk, Russian Federation, 630051
        • Municipal Healthcare Institution "City Clinical Hospital #2"
      • Novosibirsk, Russian Federation, 630087
        • Regional State Healthcare
      • Saint-Petersburg, Russian Federation, 194291
        • State Healthcare Institution
      • Saint-Petersburg, Russian Federation, 195067
        • State Educational Institution of Higher Professional Education
      • Saint-Petersburg, Russian Federation, 196247
        • Saint Petersburg State Healthcare Institution "City Hospital # 26"
  • Serbia
      • Belgrade, Serbia, 11000
        • Clinical Hospital Centre Zvezdara
      • Belgrade, Serbia, 11000
        • Emergency Centre, Clinical Centre of Serbia
      • Nis, Serbia, 18000
        • Clincal Centre Nis
      • Novi Sad, Serbia, 21000
        • Clinical Centre of Vojvodina
  • United States
    • California
      • Orange, California, United States, 92868
        • Pulmonary Consultants and Primary Care Physicians Medical Group, Inc.
      • Torrance, California, United States, 90509
        • Los Angeles Biomedical Research Institue at Harbor UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 88045
        • University Of Colorado Hospital
    • Delaware
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System
    • Florida
      • Pensacola, Florida, United States, 32504
        • Pensacola Research Consultants, Inc.
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • New Jersey
      • Somers Point, New Jersey, United States, 08244
        • South Jersey Infectious Disease
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • Metro Health Medical Center
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Tennessee
      • Memphis, Tennessee, United States, 38163
        • University of Tennessee Health Science Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female, from 18 to 90 years of age, inclusive
  • One of the following diagnoses (in which there is evidence of intraperitoneal infection) including:(a) Cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall;(b)Diverticular disease with perforation or abscess; (c) Appendiceal perforation or periappendiceal abscess; (d) Acute gastric or duodenal perforation, only if operated on >24 hours after perforation occurs; (e) Traumatic perforation of the intestine, only if operated on > 12 hours after perforation occurs; (f) Peritonitis due to perforated viscus, postoperative or spread from other focus of infection (but not spontaneous [primary] bacterial peritonitis or peritonitis associated with cirrhosis and chronic ascites).Subjects with inflammatory bowel disease or ischemic bowel disease are eligible provided there is bowel perforation; or (g) Intraabdominal abscess (including liver and spleen).
  • Subject requires surgical intervention (e.g. laparotomy, laparoscopic surgery, or percutaneous draining of an abscess) within 24 hours of (before or after) the first dose of study drug
  • If subject is to be enrolled preoperatively, the subject must have radiographic evidence of bowel perforation or intraabdominal abscess
  • Subjects who failed prior antibacterial treatment for the current cIAI can be enrolled but must: (a) have a positive culture (from an intraabdominal site) and (b) require surgical intervention. Such subjects can be enrolled before the results of the culture are known; however, if the culture is negative, study drug administration must be discontinued.
  • Willing and able to comply with all study procedures and restrictions
  • Willing and able to provide written informed consent

Exclusion Criteria:

  • Women who are pregnant, nursing, or - if of child bearing potential - not using a medically accepted, effective method of birth control (e.g. condom, oral contraceptive, indwelling intrauterine device, or sexual abstinence)
  • Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours; perforation of gastroduodenal ulcer with surgery within 24 hours (these are considered situations of peritoneal soiling before infection has become established); another intraabdominal process in which the primary etiology is not likely to be infectious.
  • Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected, necrotizing pancreatitis, or pancreatic abscess
  • cIAI managed by staged abdominal repair (STAR), open abdomen technique or any situation where infection source control is not likely to be achieved
  • Known prior to randomization to have an IAI or postoperative infection caused by pathogen(s) resistant to meropenem
  • Considered unlikely to survive the 4- to 5-week study period
  • Any rapidly-progressing disease or immediately life-threatening illness (including acute hepatic failure, respiratory failure and septic shock)
  • The need for concomitant systemic antibacterial agents (other than vancomycin or linezolid) in addition to study drug(s)
  • Moderate or severe impairment of renal function (estimated CrCl < 50 mL/min), or requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/h urine output over 24 hours)
  • The presence of hepatic disease defined as: (a) ALT or AST > 4 x ULN; (b)Total bilirubin >2 x ULN, unrelated to cholecystitis (c) Alkaline phosphatase >4 x ULN. Subjects with a value >4 x ULN and <5 x ULN are eligible if this value is historically stable.
  • Subjects with acute hepatic failure or acute decompensation of chronic hepatic failure
  • Hematocrit < 25% or hemoglobin < 8 gm/dL
  • Neutropenia with absolute neutrophil count < 1000/mm3
  • Platelet count < 75,000 /mm3. Subjects with a platelet count as low as 50,000 /mm3 are permitted if the reduction is historically stable.
  • Immunocompromising illness, including known human immunodeficiency virus (HIV) positivity or AIDS, organ (including bone marrow) transplant recipients, and hematological malignancy. Immunosuppressive therapy, including use of high-dose corticosteroid therapy (e.g. >40 mg prednisone or equivalent per day for greater than 2 weeks).
  • History of hypersensitivity reactions to cephalosporins, carbapenems, penicillins, ß-lactamase inhibitors, metronidazole, or nitroimidazole derivatives. Subjects with a history of mild skin rash, not documented to be caused by previous ß-lactam use, may be enrolled.
  • Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of study data
  • Clinically significant abnormality in baseline electrocardiogram (ECG)
  • Participation in any investigational drug or device study within 30 days prior to study entry
  • Use of systemic antibiotic therapy for IAI for 24 or more hours in the 48-hour period prior to the first dose of study drug, unless there is a documented treatment failure with such therapy
  • More than one dose of an active non-study antibacterial regimen was given postoperatively. For subjects enrolled preoperatively, no postoperative non-study antibacterial therapy is allowed
  • who previously participated in a study with CXA-101
  • Subjects who previously received imipenem, meropenem, doripenem or cefepime for the current intraabdominal infection
  • Subjects who have received disulfiram in the past 14 days or who are currently receiving probenecid.

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: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CXA 101/tazobactam and metronidazole
Drug: CXA-101/ tazobactam and metronidazole
CXA-101/tazobactam (1000/500 mg q8h) plus metronidazole (500 mg q8h) administered via IV infusion
Active Comparator: meropenem with matching saline placebo
Drug: meropenem plus saline placebo
meropenem IV infusion (1000 mg q8h) plus a matching saline placebo (q8h) administered via IV infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Clinical Response of CXA 101/Tazobactam and Metronidazole at Test of Cure (TOC) Visit in the Microbiological Modified Intent to Treat (mMITT) Analysis Population
Time Frame: Test-of-Cure Visit (7-14 days after End of Therapy [EOT])
Clinical response is complete resolution or significant improvement of all signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.
Test-of-Cure Visit (7-14 days after End of Therapy [EOT])

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Microbiological Response of CXA 101/Tazobactam and Metronidazole at the TOC Visit in the Microbiologically Evaluable (ME) Population
Time Frame: Test-of-Cure Visit (7-14 days after EOT)
Microbiological response is eradication (absence of the baseline pathogen from a suitable intra-abdominal specimen) or presumed eradication (absence of a suitable intra-abdominal specimen to culture at the TOC visit in a subject who is assessed as a clinical cure at TOC)
Test-of-Cure Visit (7-14 days after EOT)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cubist Pharmaceuticals LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Ian Friedland, MD, Cubist Pharmaceuticals LLC

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.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 25, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 20, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 25, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 17, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 22, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 25, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 27, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 7625A-012
  • CXA-IAI-10-01 (Other Identifier: Cubist Study Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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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