Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03671967
Other study ID # MOH_2018-12-25_004857
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date May 1, 2019
Est. completion date April 2026

Study information

Verified date February 2024
Source Rambam Health Care Campus
Contact Roni Bitterman, MD
Phone 972-4-7772991
Email ro_oren@rambam.health.gov.il
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Data regarding optimal treatment for extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae blood-stream infection are lacking. Observational studies show conflicting results when comparing treatment with combination beta-lactam-beta-lactamase inhibitor and carbapenems. The investigators aim to evaluate the effect of definitive treatment with meropenem vs. piperacillin-tazobactam on the outcome of patients with bacteremia due to cephalosporin-non-susceptible Enterobacteriaceae. The investigators hypothesize that piperacillin-tazobactam is non-inferior to meropenem.


Recruitment information / eligibility

Status Recruiting
Enrollment 1084
Est. completion date April 2026
Est. primary completion date January 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Adults (age = 18 years) 2. New onset BSI due to E. coli or Klebsiella spp. in one or more blood cultures associated with evidence of infection. 3. The microorganism will have to be non-susceptible to third generation cephalosporins (ceftriaxone and ceftazidime) and susceptible to both PTZ and meropenem (see microbiological methods). 4. Both community and hospital-acquired bacteremias will be included. 5. We will permit the inclusion of bacteremias due to E. coli or Klebsiella spp. with concomitant growth in blood of skin commensals considered as contaminants. Exclusion Criteria: 1. More than 72 hr. elapsed since initial blood culture taken, regardless of the time covering antibiotics were started (up to 72 hrs.). 2. Polymicrobial bacteremia. Polymicrobial bacteremia will be defined as either growth of two or more different species of microorganisms in the same blood culture, or growth of different species in two or more separate blood cultures within the same episode. 3. Patients with prior bacteremia or infection that have not completed antimicrobial therapy for the previous infectious episode. 4. Patients with septic shock at the time of enrollment and randomization, defined as at least 2 measurements of systolic blood pressure < 90 mmHg and/or use of vasopressors (dopamine>15µg/kg/min, adrenalin>0.1µg/kg/min, noradrenalin>0.1µg/kg/min, vasopressin any dose) in the 12 hours prior to randomization. In the absence of the use of vasopressors, a systolic blood pressure <90 would need to represent a deviation for the patient's known normal blood pressure. 5. BSI due to specific infections known at the time of randomization: 1. Endocarditis / endovascular infections 2. Osteomyelitis (not resected) 3. Central nervous system infections 6. Allergy to any of the study drugs confirmed by history taken by the investigator 7. Previous enrollment in this trial 8. Concurrent participation in another interventional clinical trial 9. Imminent death (researcher's assessment of expected death within 48 hrs. of recruitment)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Piperacillin/tazobactam
4.5 grams QID
Meropenem
1 gram TID

Locations

Country Name City State
Canada Jewish Genral Hospital Montreal Quebec
Canada McGill University Health Centre Montreal, Quebec
Canada Eastern Health Saint John's Newfoundland and Labrador
Canada Surrey Memorial Hospital - Fraser Health Authority Surrey British Columbia
Israel Soroka Medical Center Be'er Sheva
Israel Rambam Health Care Campus Haifa
Israel Hadassah Medical Center Jerusalem
Israel Meir Medical Center Kfar Saba
Israel Rabin Medical Center, Beilinson Campus Petah tikva
Israel Sheba Medical Center (Tel HaShomer) Tel Aviv
Israel Sourasky Medical Center Tel Aviv

Sponsors (11)

Lead Sponsor Collaborator
Rambam Health Care Campus Canadian Institutes of Health Research (CIHR), Hadassah Medical Organization, Jewish General Hospital, McGill University Health Centre/Research Institute of the McGill University Health Centre, Meir Medical Center, Rabin Medical Center, Soroka University Medical Center, Tel Aviv Medical Center, The Chaim Sheba Medical Center, University of Modena and Reggio Emilia

Countries where clinical trial is conducted

Canada,  Israel, 

Outcome

Type Measure Description Time frame Safety issue
Primary All-cause mortality 30 days from randomization
Primary Treatment failure death OR fever > 38°C in the last 48 hours OR lack of resolution of symptoms attributed to the focus of infection OR Sequential Failure Organ Assessment (SOFA) score increasing OR positive blood cultures by the time point assessed 7 days from randomization
Secondary All-cause mortality 14 and 90 days from randomization
Secondary Treatment failure death OR fever > 38°C in the last 48 hours OR lack of resolution of symptoms attributed to the focus of infection OR Sequential Failure Organ Assessment (SOFA) score increasing OR positive blood cultures by the time point assessed 14 days and 30 days from randomization
Secondary Microbiological failure Repeat positive blood cultures with index pathogen on day 4 or later from randomization 7 days and 14 days from randomization
Secondary Recurrent positive blood cultures (relapse) recurrent positive blood cultures with the index pathogen after prior sterilization of blood cultures or after end of treatment 30 days and 90 days from randomization
Secondary Clostridium difficile associated diarrhea 90 days from randomization
Secondary Clinically or microbiologically documented infection other than Gram-negative bacteremia 90 days from randomization
Secondary Number of hospital re-admissions 90 days from randomization
Secondary Development of resistance clinical isolates resistant to piperacillin/tazobactam and meropenem and any carbapenem-resistant bacteria 90 days from randomization
Secondary Carriage of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE carbapenem-resistant Enterobacteriaceae in-hospital detected by weekly rectal surveillance of carriage while in-hospital 90 days from randomization
Secondary Total in-hospital days 30 days and 90 days from randomization
Secondary Total antibiotic days 30 days and 90 days from randomization
Secondary Adverse events diarrhea, liver function test abnormalities, antibiotic rash or other immediate-type allergy, acute kidney injury defined according to RIFLE criteria 30 days from randomization
See also
  Status Clinical Trial Phase
Completed NCT03894046 - Study to Evaluate the Efficacy and Safety of Intravenous Sulbactam-ETX2514 in the Treatment of Patients With Infections Caused by Acinetobacter Baumannii-calcoaceticus Complex Phase 3
Active, not recruiting NCT03354338 - Amoxicillin to Prevent Bacteria and Inflammatory Biomarkers After Intensive Periodontal Therapy Phase 2
Withdrawn NCT02543957 - Factors Associated With Increased Risk of Bacteremia and Cholangitis in ERCP With Cholangioscopy
Completed NCT02210169 - RCT of Continuous Versus Intermittent Infusion of Vancomycin in Neonates N/A
Completed NCT01410578 - The Value of sTREM-1, PCT, and CRP as Markers for the Detection of Sepsis and Bacteremia Among Patients With a FUO N/A
Completed NCT00609375 - Efficacy of Cefepime Continuous Infusion Versus an Intermittent Dosing Regimen Phase 4
Terminated NCT00428051 - Colombia Epidemiologic Surveillance Study N/A
Terminated NCT00108433 - Linezolid in the Treatment of Hemodialysis Patients With Catheter-Related Gram-Positive Bloodstream Infections Phase 3
Completed NCT00177736 - Pharmacodynamic Parameters of Two Different Doses of Cefepime Phase 4
Completed NCT00571259 - Prophylactic Antimicrobial Catheter Lock Phase 4
Completed NCT00027248 - Safety and Efficacy of MBI 226 for the Prevention of Central Venous Catheter-Related Bloodstream Infections Phase 3
Completed NCT05585463 - Safety of Acupuncture and Intracutaneous Needles in Pediatric Cancer Patients: a Retrospective Study (ACUSAFE2021)
Recruiting NCT05950984 - Medical Device (MD) Derived Pharmacokinetic (PK) Parameters for Vancomycin (MD-PK)
Completed NCT03148769 - Spanish Bacteriemia Cohort 2016: Epidemiology, Clinical Management and Prognosis Factors
Completed NCT02536352 - Effect of Supplementation of Fluoride on Maternal Periodontal Health, Preterm Delivery, and Perinatal Well-Being Early Phase 1
Completed NCT02869191 - Blood Cultures's Profitability in Intensive Care Unit
Terminated NCT01734694 - Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients Phase 4
Completed NCT01179022 - Incidence of Bacteremia Following Argon Plasma Coagulation in Patients With Endobronchial Lesions N/A
Recruiting NCT00404625 - Infections Caused by ESbL-Producing Enterobacteriaceae in Italy N/A
Completed NCT00398411 - Moxifloxacin in the Prevention of Bacteremia After High-dose Chemotherapy and Transplantation of Peripheral Stem Cells Phase 3