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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT05258851
Other study ID # RAC#2211247
Secondary ID
Status Terminated
Phase Phase 3
First received
Last updated
Start date June 1, 2022
Est. completion date January 28, 2024

Study information

Verified date June 2024
Source King Faisal Specialist Hospital & Research Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 29
Est. completion date January 28, 2024
Est. primary completion date April 12, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 85 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Ceftazidime-avibactam
Experimental
Colistin
Control

Locations

Country Name City State
Saudi Arabia King Faisal Specialist Hospital & Research Centre Riyadh

Sponsors (1)

Lead Sponsor Collaborator
King Faisal Specialist Hospital & Research Center

Country where clinical trial is conducted

Saudi Arabia, 

Outcome

Type Measure Description Time frame Safety issue
Primary 28-day mortality Death 28 days from randomization
Secondary 14-day mortality Death 14 days from randomization
Secondary 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.
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.
For bloodstream infection: 1+ documented two negative blood cultures with source removal if applicable.
For complicated intra-abdominal infection: 1+ resolution or decreasing size of intra-abdominal collections with source control if applicable.
For complicated skin and soft tissue infection: 1+ resolution of signs and symptoms plus surgical drainage or debridement if applicable.
For complicated urinary tract infection: 1+ resolution of signs and symptoms and source removal if applicable.
EOT at 7-14 days from randomization and TOC 7 days after completion of treatment
Secondary 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:
Eradication (successful microbiological response): Baseline pathogen no longer present in the culture(s) that indicated the use of study drugs.
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.
Persistence (failure of microbiological response): Presence of baseline pathogen in the culture that indicated the use of study drugs.
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.
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.
EOT at 7-14 days from randomization and TOC 7 days after completion of treatment
Secondary Time to weaning from mechanical ventilation at day 28 Number of days not receiving mechanical ventilation 28 days from randomization
Secondary Requirement for renal replacement therapy at day 28 New start of renal replacement therapy 28 days from randomization
Secondary Intensive care unit (ICU) length of stay, censored at 28 days Duration of stay inside the ICU 28 days from randomization
Secondary Days alive and out of the ICU, censored at 28 days Number of days alive and outside the ICU 28 days from randomization
Secondary Drug-related adverse events Acute kidney injury, seizures, leukopenia, thrombocytopenia, allergic reaction, diarrhea, clostridium difficile infection. 28 days from randomization
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