PipEracillin Tazobactam versus mERoPENem for treatment of bloodstream infections caused by cephalosporin-resistant Enterobacteriaceae - a non-inferiority randomized controlled trial (PETERPEN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Di Modena

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

18 Nov 2025 → ongoing

Decision date (initial)

2025-09-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the effect of definitive treatment with meropenem vs. PTZ on the outcome of patients with bacteremia due to third-generation cephalosporin-non-susceptible (but PTZ
susceptible) E. coli, K. pneumoniae or other Klebsiella spp. (assumed ESBL-E), and SPICE-M organisms: Serratia marcescens, Providencia spp., Morganella morganii, Citrobacter freundii, and Enterobacter spp. We aim to prove the hypothesis that PTZ is non-inferior to meropenem.

Conditions and MedDRA coding

Patients with bacteremia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Adults (age ≥ 18 years) 2. New onset BSI due to E. coli,Klebsiella spp., Serratia marcescens, Providencia spp., Morganella morganii, Citrobacter freundii, and Enterobacter 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 study pathogens with concomitant growth in blood of skin commensals considered as contaminants.

Exclusion criteria 1

1. 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: a. Endocarditis / endovascular infections b. Osteomyelitis (not resected) c. 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) or patient in palliative care

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Treatment failure at day 7 from randomization. Treatment modifications before day 7 will be discouraged, but they will be allowed according to treating physicians’ discretion

Secondary endpoints 2

1. •All-cause mortality 14,30,90days •Treatment failure 7,14,30days •Microbiological failure 7,14days •Relapse 30,90days •Clostridium difficile associated diarrhea till 90days •Development of either clinically or microbiologically documented infection other than Gram-negative bacteremia within 90days •Number of hospital re-admissions until day90
2. •Development of resistance •Carriage of carbapenemase-producing Enterobacteriaceae and non-CPE CRE in-hospital till day90 •Total in-hospital days within 30,90days •Total antibiotic days within 30,90days •Adverse events at 30days

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Di Modena

Sponsor organisation

Azienda Ospedaliero Universitaria Di Modena

Address

Largo Del Pozzo 71

City

Modena

Postcode

41124

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Cristina Mussini

Public contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Cristina Mussini

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications