- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05258851
Ceftazidime-Avibactam Use in Critically Ill Patients With Carbapenem-Resistant Enterobacteriaceae Infections (AVI-ICU)
Ceftazidime-Avibactam Versus Colistin in Critically Ill Patients With Carbapenem-Resistant Enterobacteriaceae Infections (AVI-ICU): A Non-Inferiority Randomized Clinical Trial
Carbapenem-Resistant Enterobacteriaceae (CRE) infections are a growing national and international challenge in healthcare settings. This is not only due to the rapid spread of resistance and paucity of options of targeted-antimicrobial agents, but also owing to the high mortality of patients infected with CRE reaching up to 50% as per the Centers of Disease Control and Prevention.
Colistin-based combination regimens have been the mainstay for treating CRE-related infections. Ceftazidime-avibactam is a beta-lactamase inhibitor combination, a novel antibiotic, which recently showed a better clinical and microbiological cure against CRE along with the potential to reduce mortality and nephrotoxicity in comparison to colistin-based regimens in observational studies. However, randomized clinical trials are lacking.
This non-inferiority randomized controlled study aims to assess the efficacy and safety of ceftazidime-avibactam-based regimens in critically ill patients with CRE infections in comparison to colistin-based regimens.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Riyadh, Saudi Arabia
- King Faisal Specialist Hospital & Research Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients aged ≥ 18 years.
- Admitted to an intensive care unit (ICU).
- Patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), complicated urinary tract infection (cUTI), bacteremia, complicated intraabdominal infection (cIAI), and complicated skin and soft tissue infection (cSSTI).
- Confirmed infection with CRE, based on a culture and sensitivity obtained within the past 72 hours of study enrollment.
- Suspected CRE infection according to one of the following: (1) positive Xpert Carba-R test screening for blaKPC or blaOXA-48 or blaNDM or blaVIM or blaIMI assessed on the admission to the ICU, (2) positive culture for CRE obtained within 3 months from time of enrollment.
Exclusion Criteria:
- Acute Physiology and Chronic Health Evaluation II (APACHE II) score more than 30
- known significant hypersensitivity reaction to beta-lactam antibiotics or colistin
- Positive culture for Stenotrophomonas maltophilia or Acinetobacter baumannii within the current hospitalization.
- Patients received the study intervention or control for more than 24 hours before the intended randomization.
- Patient/substitute decision-maker or caring physician's refusal to enroll in the study.
- Patient with concomitant suspected or confirmed meningitis.
- Pregnancy.
- Cystic fibrosis.
- Patients with Do Not Attempt to Resuscitate (DNAR) code status.
- Prior knowledge that the index CRE pathogen was resistant to colistin (MIC >2 μg/ml) or ceftazidime-avibactam (MIC > 8 μg/ml) before randomization.
- Objective clinical evidence for any of the following infections that necessitate study therapy for >14 days: endovascular infection, including endocarditis, osteomyelitis, prosthetic joint infection, meningitis, and/or other central nervous system infections
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Ceftazidime-avibactam
Ceftazidime-avibactam 2.5 grams intravenous (IV) every 8 hours infused over two hours for a duration of 7-14 days, with dose adjustment for renal impairment according to the FDA prescribing information.
Patients who have a positive Xpert Carb-R screening test or culture for CRE with metallo-beta-lactamases will receive aztreonam added to ceftazidime-avibactam.
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Experimental
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Active Comparator: Colistin
Colistin (9-million-unit loading dose IV followed with 9 million units IV daily divided into 3 doses), for 7 to 14 days.
Patients with renal impairment will receive antibiotics with adjusted doses based on their glomerular filtration rate or the use and type of renal replacement therapy according to the 2019 International Consensus Guidelines for the Optimal Use of the Polymyxins.
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Control
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
28-day mortality
Time Frame: 28 days from randomization
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Death
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28 days from randomization
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
14-day mortality
Time Frame: 14 days from randomization
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Death
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14 days from randomization
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Number of patients with clinical success at end of therapy (EOT) at day 7-14 from randomization and test of cure (TOC) 7 days after completion of treatment
Time Frame: EOT at 7-14 days from randomization and TOC 7 days after completion of treatment
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Defined as: 1- Alive, fever or hypothermia resolution, WBC counts normalization, hemodynamic stability with MAP ≥65 mmHg without vasopressors support.
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EOT at 7-14 days from randomization and TOC 7 days after completion of treatment
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Number of patients with microbiological response at the EOT at days 7-14 from randomization and TOC 7 days after completion of treatment
Time Frame: EOT at 7-14 days from randomization and TOC 7 days after completion of treatment
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Defined as:
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EOT at 7-14 days from randomization and TOC 7 days after completion of treatment
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Time to weaning from mechanical ventilation at day 28
Time Frame: 28 days from randomization
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Number of days not receiving mechanical ventilation
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28 days from randomization
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Requirement for renal replacement therapy at day 28
Time Frame: 28 days from randomization
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New start of renal replacement therapy
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28 days from randomization
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Intensive care unit (ICU) length of stay, censored at 28 days
Time Frame: 28 days from randomization
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Duration of stay inside the ICU
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28 days from randomization
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Days alive and out of the ICU, censored at 28 days
Time Frame: 28 days from randomization
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Number of days alive and outside the ICU
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28 days from randomization
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Drug-related adverse events
Time Frame: 28 days from randomization
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Acute kidney injury, seizures, leukopenia, thrombocytopenia, allergic reaction, diarrhea, clostridium difficile infection.
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28 days from randomization
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Collaborators and Investigators
Investigators
- Principal Investigator: Zainab Al Duhailib, King Faisal Specialist Hospital & Research Center
- Principal Investigator: Hakeam Hakeam, King Faisal Specialist Hospital & Research Center
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
Additional Relevant MeSH Terms
- Pathologic Processes
- Disease Attributes
- Gram-Negative Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Infections
- Communicable Diseases
- Critical Illness
- Enterobacteriaceae Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Anti-Bacterial Agents
- beta-Lactamase Inhibitors
- Third Generation Cephalosporins
- Beta Lactam Antibiotics
- Colistin
- Avibactam
- Ceftazidime
- Avibactam, ceftazidime drug combination
Other Study ID Numbers
- RAC#2211247
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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