PipEracillin Tazobactam Versus mERoPENem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae (PETERPEN)

NCT03671967 | Recruiting Phase 4 DMC

• 1 other identifier: MOH_2018-12-25_004857
• Study Type: interventional
• Target: 1,084
• Locations: 2 countries
• Sites: 14

Brief 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.

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

  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

• Treatment failure

  14 days and 30 days from randomization

• Microbiological failure

  7 days and 14 days from randomization

• Recurrent positive blood cultures (relapse)

  30 days and 90 days from randomization

• Clostridium difficile associated diarrhea

  90 days from randomization

Study Arms (2)

piperacillin tazobactam

EXPERIMENTAL

Drug: Piperacillin/tazobactam

meropenem

ACTIVE COMPARATOR

Drug: Meropenem

Interventions

Piperacillin/tazobactam DRUG

4.5 grams QID

piperacillin tazobactam

Meropenem DRUG

1 gram TID

meropenem

Eligibility Criteria

• Age: 18 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 E. coli or Klebsiella 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)

Sponsors & Collaborators

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

Study Sites (14)

University of Calgary, Cumming School of Medicine, O'Brien Institute for Public Health

Calgary, Alberta, T2N 4Z6, Canada

RECRUITING

Surrey Memorial Hospital - Fraser Health Authority

Surrey, British Columbia, Canada

RECRUITING

Eastern Health

St. John's, Newfoundland and Labrador, Canada

RECRUITING

Kingston General Hospital

Kingston, Ontario, Canada

RECRUITING

Jewish Genral Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

RECRUITING

Rambam Health Care Campus

Haifa, Israel, 3435306, Israel

RECRUITING

Soroka Medical Center

Beersheba, Israel

RECRUITING

Hadassah Medical Center

Jerusalem, Israel

RECRUITING

Meir Medical Center

Kfar Saba, Israel

RECRUITING

Sanz Medical Center-Laniado Hospital

Netanya, 42150, Israel

RECRUITING

Rabin Medical Center, Beilinson Campus

Petah Tikva, Israel

RECRUITING

Sheba Medical Center (Tel HaShomer)

Tel Aviv, Israel

RECRUITING

Sourasky Medical Center

Tel Aviv, Israel

RECRUITING

Related Publications (1)

• Bitterman R, Koppel F, Mussini C, Geffen Y, Chowers M, Rahav G, Nesher L, Ben-Ami R, Turjeman A, Huberman Samuel M, Cheng MP, Lee TC, Leibovici L, Yahav D, Paul M. Piperacillin-tazobactam versus meropenem for treatment of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacteriaceae: a study protocol for a non-inferiority open-label randomised controlled trial (PeterPen). BMJ Open. 2021 Feb 8;11(2):e040210. doi: 10.1136/bmjopen-2020-040210.

  PMID: 33558347 DERIVED

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

• Roni Bitterman, MD

  Rambam Health Care Campus

  PRINCIPAL INVESTIGATOR

• Mical Paul, MD

  Rambam Health Care Campus

  STUDY DIRECTOR

• Leonard Leibovici, MD

  Rabin Medical Center

  STUDY DIRECTOR

• Cristina Mussini, MD

  University of Modena and Reggio Emilia

  STUDY DIRECTOR

• Noa Eliakim-Raz, MD

  Rabin Medical Center, Beilinson Campus

  STUDY DIRECTOR

Central Study Contacts

Mical Paul, MD

CONTACT

972-4-7772991; m_paul@rambam.health.gov.il

Roni Bitterman, MD

CONTACT

972-4-7772991; ro_oren@rambam.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open-label randomized controlled trial

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 14, 2018
• Study Start: May 1, 2019
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 1, 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 ro\ oren@rambam.health.gov.il

Locations

IL (8); CA (6)