Ceftazidime-Avibactam Use in Critically Ill Patients With Carbapenem-Resistant Enterobacteriaceae Infections

NCT ID: NCT05258851

Last Updated: 2024-06-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-01
• Study Completion Date: 2024-01-28

Brief Summary

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.

Conditions

Carbapenem-Resistant Enterobacteriaceae Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Ceftazidime-avibactam

Intervention Type: DRUG

Experimental

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.

Group Type: ACTIVE_COMPARATOR

Colistin

Intervention Type: DRUG

Control

Interventions

Ceftazidime-avibactam

Experimental

Intervention Type: DRUG

Colistin

Control

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients aged ≥ 18 years.

2. Admitted to an intensive care unit (ICU).

3. 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).

4. Confirmed infection with CRE, based on a culture and sensitivity obtained within the past 72 hours of study enrollment.

5. 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

1. Acute Physiology and Chronic Health Evaluation II (APACHE II) score more than 30

2. known significant hypersensitivity reaction to beta-lactam antibiotics or colistin

3. Positive culture for Stenotrophomonas maltophilia or Acinetobacter baumannii within the current hospitalization.

4. Patients received the study intervention or control for more than 24 hours before the intended randomization.

5. Patient/substitute decision-maker or caring physician's refusal to enroll in the study.

6. Patient with concomitant suspected or confirmed meningitis.

7. Pregnancy.

8. Cystic fibrosis.

9. Patients with Do Not Attempt to Resuscitate (DNAR) code status.

10. Prior knowledge that the index CRE pathogen was resistant to colistin (MIC >2 μg/ml) or ceftazidime-avibactam (MIC > 8 μg/ml) before randomization.

11. 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King Faisal Specialist Hospital & Research Center

OTHER

Sponsor Role: lead

Responsible Party

Zainab Alduhailib

Critical Care Medicine Consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zainab Al Duhailib

Role: PRINCIPAL_INVESTIGATOR

King Faisal Specialist Hospital & Research Center

Hakeam Hakeam

Role: PRINCIPAL_INVESTIGATOR

King Faisal Specialist Hospital & Research Center

Locations

King Faisal Specialist Hospital & Research Centre

Riyadh, , Saudi Arabia

Countries

Saudi Arabia

Other Identifiers

RAC#2211247

Identifier Type: -

Identifier Source: org_study_id