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

NCT ID: NCT03671967

Last Updated: 2025-08-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1084 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-01
• Study Completion Date: 2027-04-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

piperacillin tazobactam

Group Type: EXPERIMENTAL

Piperacillin/tazobactam

Intervention Type: DRUG

4.5 grams QID

meropenem

Group Type: ACTIVE_COMPARATOR

Meropenem

Intervention Type: DRUG

1 gram TID

Interventions

Piperacillin/tazobactam

4.5 grams QID

Intervention Type: DRUG

Meropenem

1 gram TID

Intervention Type: DRUG

Eligibility Criteria

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)

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

Sponsors

Rabin Medical Center

OTHER

Sponsor Role: collaborator

University of Modena and Reggio Emilia

OTHER

Sponsor Role: collaborator

Tel Aviv Medical Center

OTHER

Sponsor Role: collaborator

Meir Medical Center

OTHER

Sponsor Role: collaborator

Soroka University Medical Center

OTHER

Sponsor Role: collaborator

The Chaim Sheba Medical Center

OTHER

Sponsor Role: collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: collaborator

Jewish General Hospital

OTHER

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Hadassah Medical Organization

OTHER

Sponsor Role: collaborator

Rambam Health Care Campus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roni Bitterman, MD

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Campus

Mical Paul, MD

Role: STUDY_DIRECTOR

Rambam Health Care Campus

Leonard Leibovici, MD

Role: STUDY_DIRECTOR

Rabin Medical Center

Cristina Mussini, MD

Role: STUDY_DIRECTOR

University of Modena and Reggio Emilia

Noa Eliakim-Raz, MD

Role: STUDY_DIRECTOR

Rabin Medical Center, Beilinson Campus

Locations

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

Calgary, Alberta, Canada

Site Status: RECRUITING

Surrey Memorial Hospital - Fraser Health Authority

Surrey, British Columbia, Canada

Site Status: RECRUITING

Eastern Health

St. John's, Newfoundland and Labrador, Canada

Site Status: RECRUITING

Kingston General Hospital

Kingston, Ontario, Canada

Site Status: RECRUITING

Jewish Genral Hospital

Montreal, Quebec, Canada

Site Status: RECRUITING

McGill University Health Centre

Montreal, Quebec, , Canada

Site Status: RECRUITING

Rambam Health Care Campus

Haifa, Israel, Israel

Site Status: RECRUITING

Soroka Medical Center

Beersheba, , Israel

Site Status: RECRUITING

Hadassah Medical Center

Jerusalem, , Israel

Site Status: RECRUITING

Meir Medical Center

Kfar Saba, , Israel

Site Status: RECRUITING

Sanz Medical Center-Laniado Hospital

Netanya, , Israel

Site Status: RECRUITING

Rabin Medical Center, Beilinson Campus

Petah Tikva, , Israel

Site Status: RECRUITING

Sheba Medical Center (Tel HaShomer)

Tel Aviv, , Israel

Site Status: RECRUITING

Sourasky Medical Center

Tel Aviv, , Israel

Site Status: RECRUITING

Countries

Canada; Israel

Central Contacts

Mical Paul, MD

Role: CONTACT

m_paul@rambam.health.gov.il

972-4-7772991

Roni Bitterman, MD

Role: CONTACT

ro_oren@rambam.health.gov.il

972-4-7772991

Facility Contacts

John Conly, MD

Role: primary

jconly@ucalgary.ca

Kevin Afra, MD

Role: primary

Kevin.Afra@fraserhealth.ca

Peter Daley, MD

Role: primary

pkd336@mun.ca

Tony Bai, MD

Role: primary

tony.bai@queensu.ca

Barbara Antuna Puente, MD

Role: backup

Barbarbara.antunapuente@queensu.ca

Leighanne Parkes, MD

Role: primary

Leighanne Parkes

Role: backup

leighanne.parkes@mcgill.ca

Todd Lee, MD

Role: primary

Role: backup

todd.lee@mcgill.ca

Roni Bitterman

Role: primary

ro_oren@rambam.health.gov.il

47772991

Lior Nesher, MD

Role: primary

nesherke@bgu.ac.il

Jacob strahilevitz, MD

Role: primary

jstrahilevitz@hadassah.org.il

Michal Chowers, MD

Role: primary

michalch@clalit.org.il

Candice Datnow, MD

Role: primary

cdatnow@laniado.org.il

Alaa Atamna, MD

Role: primary

a.atamna86@gmail.com

Dafna Yahav, MD

Role: primary

dafna.yahav@gmail.com

Ronen Ben-Ami, MD

Role: primary

ronenba@tlvmc.gov.il

References

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.

Reference Type: DERIVED

PMID: 33558347 (View on PubMed)

Other Identifiers

MOH_2018-12-25_004857

Identifier Type: -

Identifier Source: org_study_id