PipEracillin/Tazobactam Versus mERoPENem for Treatment of AmpC Producing Blood Stream Infections

NCT05355350 | Withdrawn Phase 4 DMC

• 1 other identifier: 0295-18-RMB
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

Data regarding optimal treatment for extended-spectrum beta-lactamase (ESBL) producing Enterobacterales bloodstream 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.

Conditions

Beta Lactam Resistant Bacterial Infection; Enterobacteriaceae Infections; Bacteremia

Keywords

bacteremia; enterobacteriaceae; extended spectrum beta-lactamase; meropenem; piperacillin tazobactam

Outcome Measures

Primary Outcomes (2)

• All-cause mortality

  Primary Outcome Measure

  30 days from randomization

• 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 Outcomes (12)

• All-cause mortality

  14 and 90 days from randomization]

• Number of participants with treatment failure

  14 days and 30 days from randomization

• Number of participants with microbiological failure

  7 days and 14 days from randomization

• Number of participants with recurrent positive blood cultures (relapse)

  30 days and 90 days from randomization

• Number of participants with Clostridium difficile associated diarrhea

  90 days from randomization

Study Arms (2)

piperacillin tazobactam

EXPERIMENTAL

Drug: Piperacillin / Tazobactam Injection

meropenem

ACTIVE COMPARATOR

Drug: Meropenem

Interventions

Piperacillin / Tazobactam Injection DRUG

4.5 grams QID

piperacillin tazobactam

Meropenem DRUG

1 gram TID

meropenem

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (age ≥ 18 years)
• New onset BSI due to Serratia marcescens, Providencia spp., Morganella morganii, Citrobacter freundii, and Enterobacter spp.in one or more blood cultures associated with evidence of infection.
• 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).
• Both community and hospital-acquired bacteremias will be included.

You may not qualify if:

• More than 72 hr. elapsed since initial blood culture taken, regardless of the time covering antibiotics were started (up to 72 hrs.).
• 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.
• Patients with prior bacteremia or infection that have not completed antimicrobial therapy for the previous infectious episode.
• 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.
• BSI due to specific infections known at the time of randomization:
• Endocarditis / endovascular infections
• Osteomyelitis (not resected)
• Central nervous system infections
• Allergy to any of the study drugs confirmed by history taken by the investigator
• Previous enrollment in this trial
• Concurrent participation in another interventional clinical trial
• Imminent death (researcher's assessment of expected death within 48 hrs. of recruitment) or patient in palliative care

Sponsors & Collaborators

• Rambam Health Care Campus: lead
• The Chaim Sheba Medical Center: collaborator
• Rabin Medical Center: collaborator
• Hadassah Medical Organization: collaborator

Study Sites (4)

Rambam Health Care Campus

Haifa, Israel

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Rabin Medical Center, Beilinson Hospital

Petah Tikva, Israel

Location

Sheba Tel HaShomer Medical Campus

Ramat Gan, Israel

Location

MeSH Terms

Conditions

Enterobacteriaceae Infections; Bacteremia

Interventions

Piperacillin, Tazobactam Drug Combination; Meropenem

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tazobactam; Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Thienamycins; Carbapenems

Study Officials

• Mical Paul, MD

  Rambam Health Care Campus

  PRINCIPAL INVESTIGATOR

• Dafna Yahav, MD

  Sheba Tel HaShomer Medical Campus

  PRINCIPAL INVESTIGATOR

• Alaa Atamna, MD

  Rabin Medical Center, Beilinson Campus

  PRINCIPAL INVESTIGATOR

• Roni Bitterman, MD

  Rambam Health Care Campus

  STUDY DIRECTOR

• Noa Eliakim-Raz, MD

  Rabin Medical Center, Beilinson Campus

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Mical Paul, MD

Study Record Dates

• First Submitted: April 4, 2022
• First Posted: May 2, 2022
• Study Start: July 1, 2022
• Primary Completion: July 21, 2025
• Study Completion: July 21, 2025
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: following publication and for unlimited time
• Access Criteria: proposals should be sent to the principal investigator at m\ paul@rambam.health.gov.il

Locations

IL (4)