A Phase 3 interventional study of Ceftazidime-avibactam and Colistin in Carbapenem-Resistant Enterobacteriaceae Infection, sponsored by King Faisal Specialist Hospital & Research Center. Terminated at 1 site in Saudi Arabia. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-06-14.
Sponsored by King Faisal Specialist Hospital & Research Center · Phase 3, Interventional, and Treatment
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.
1,924 studies on the registry are indexed under Critical Illness; 465 are open to participants now.
This study's enrollment of 29 is below the median of 90 across 1,003 interventional studies indexed under Critical Illness.
Browse Critical Illness studies →King Faisal Specialist Hospital & Research Center is the lead sponsor of 99 studies on the registry; 18 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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.
Drug: Ceftazidime-avibactam
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.
Drug: Colistin
Experimental
Control
28-day mortality
Death
Time frame: 28 days from randomization
14-day mortality
Death
Time frame: 14 days from randomization
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
Defined as: 1- Alive, fever or hypothermia resolution, WBC counts normalization, hemodynamic stability with MAP ≥65 mmHg without vasopressors support. 1. For HAP or VAP: 1+ improving respiratory status including improving PaO2/FiO2 ratio from baseline, decreasing FiO2 and PEEP or extubation or source control for empyema. 2. For bloodstream infection: 1+ documented two negative blood cultures with source removal if applicable. 3. For complicated intra-abdominal infection: 1+ resolution or decreasing size of intra-abdominal collections with source control if applicable. 4. For complicated skin and soft tissue infection: 1+ resolution of signs and symptoms plus surgical drainage or debridement if applicable. 5. For complicated urinary tract infection: 1+ resolution of signs and symptoms and source removal if applicable.
Time frame: EOT at 7-14 days from randomization and TOC 7 days after completion of treatment
Number of patients with microbiological response at the EOT at days 7-14 from randomization and TOC 7 days after completion of treatment
Defined as: 1. Eradication (successful microbiological response): Baseline pathogen no longer present in the culture(s) that indicated the use of study drugs. 2. Presumed eradication (successful microbiological response): Patient deemed a clinical cure as assessed by the adjudication committee at EOT and TOC, and repeat culture that indicated enrollment in the study is not available. 3. Persistence (failure of microbiological response): Presence of baseline pathogen in the culture that indicated the use of study drugs. 4. Presumed persistence (failure of microbiological response): Patients deemed a clinical failure as assessed by the adjudication committee at EOT and TOC, and specimen is not available. 5. Indeterminate: Any culture that cannot be classified into one of the above categories, or the patient was an indeterminate clinical response and no cultures were taken.
Time frame: EOT at 7-14 days from randomization and TOC 7 days after completion of treatment
Time to weaning from mechanical ventilation at day 28
Number of days not receiving mechanical ventilation
Time frame: 28 days from randomization
Requirement for renal replacement therapy at day 28
New start of renal replacement therapy
Time frame: 28 days from randomization
Intensive care unit (ICU) length of stay, censored at 28 days
Duration of stay inside the ICU
Time frame: 28 days from randomization
Days alive and out of the ICU, censored at 28 days
Number of days alive and outside the ICU
Time frame: 28 days from randomization
Drug-related adverse events
Acute kidney injury, seizures, leukopenia, thrombocytopenia, allergic reaction, diarrhea, clostridium difficile infection.
Time frame: 28 days from randomization
Plan to share: No
No publications or documents are linked to this record.
Ran from Jun 2022 to primary completion in Apr 2023, 10 months.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Jun 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
King Faisal Specialist Hospital & Research Center