Ignite Creation Date:
2025-12-25 @ 12:31 AM
Ignite Modification Date:
2026-01-07 @ 7:40 AM
Study NCT ID:
NCT03671967
Status:
RECRUITING
Last Update Posted:
2025-08-01
First Post:
2018-09-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PipEracillin Tazobactam Versus mERoPENem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae (PETERPEN)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D004756', 'term': 'Enterobacteriaceae Infections'}, {'id': 'D016470', 'term': 'Bacteremia'}], 'ancestors': [{'id': 'D016905', 'term': 'Gram-Negative Bacterial Infections'}, {'id': 'D001424', 'term': 'Bacterial Infections'}, {'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D018805', 'term': 'Sepsis'}, {'id': 'D018746', 'term': 'Systemic Inflammatory Response Syndrome'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077725', 'term': 'Piperacillin, Tazobactam Drug Combination'}, {'id': 'D000077731', 'term': 'Meropenem'}], 'ancestors': [{'id': 'D000078142', 'term': 'Tazobactam'}, {'id': 'D010397', 'term': 'Penicillanic Acid'}, {'id': 'D010406', 'term': 'Penicillins'}, {'id': 'D047090', 'term': 'beta-Lactams'}, {'id': 'D007769', 'term': 'Lactams'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D010878', 'term': 'Piperacillin'}, {'id': 'D000667', 'term': 'Ampicillin'}, {'id': 'D010400', 'term': 'Penicillin G'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D004338', 'term': 'Drug Combinations'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}, {'id': 'D013845', 'term': 'Thienamycins'}, {'id': 'D015780', 'term': 'Carbapenems'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'open-label randomized controlled trial'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 1084}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2019-05-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2027-04-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-29', 'studyFirstSubmitDate': '2018-09-12', 'studyFirstSubmitQcDate': '2018-09-12', 'lastUpdatePostDateStruct': {'date': '2025-08-01', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-09-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-01-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'All-cause mortality', 'timeFrame': '30 days from randomization'}, {'measure': 'Treatment failure', 'timeFrame': '7 days from randomization', 'description': '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'}], 'secondaryOutcomes': [{'measure': 'All-cause mortality', 'timeFrame': '14 and 90 days from randomization'}, {'measure': 'Treatment failure', 'timeFrame': '14 days and 30 days from randomization', 'description': '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'}, {'measure': 'Microbiological failure', 'timeFrame': '7 days and 14 days from randomization', 'description': 'Repeat positive blood cultures with index pathogen on day 4 or later from randomization'}, {'measure': 'Recurrent positive blood cultures (relapse)', 'timeFrame': '30 days and 90 days from randomization', 'description': 'recurrent positive blood cultures with the index pathogen after prior sterilization of blood cultures or after end of treatment'}, {'measure': 'Clostridium difficile associated diarrhea', 'timeFrame': '90 days from randomization'}, {'measure': 'Clinically or microbiologically documented infection other than Gram-negative bacteremia', 'timeFrame': '90 days from randomization'}, {'measure': 'Number of hospital re-admissions', 'timeFrame': '90 days from randomization'}, {'measure': 'Development of resistance', 'timeFrame': '90 days from randomization', 'description': 'clinical isolates resistant to piperacillin/tazobactam and meropenem and any carbapenem-resistant bacteria'}, {'measure': 'Carriage of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE carbapenem-resistant Enterobacteriaceae in-hospital', 'timeFrame': '90 days from randomization', 'description': 'detected by weekly rectal surveillance of carriage while in-hospital'}, {'measure': 'Total in-hospital days', 'timeFrame': '30 days and 90 days from randomization'}, {'measure': 'Total antibiotic days', 'timeFrame': '30 days and 90 days from randomization'}, {'measure': 'Adverse events', 'timeFrame': '30 days from randomization', 'description': 'diarrhea, liver function test abnormalities, antibiotic rash or other immediate-type allergy, acute kidney injury defined according to RIFLE criteria'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['bacteremia', 'enterobacteriaceae', 'extended spectrum beta-lactamase', 'meropenem', 'piperacillin tazobactam'], 'conditions': ['Beta Lactam Resistant Bacterial Infection', 'Enterobacteriaceae Infections', 'Bacteremia']}, 'referencesModule': {'references': [{'pmid': '33558347', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Adults (age ≥ 18 years)\n2. New onset BSI due to E. coli or Klebsiella spp. in one or more blood cultures associated with evidence of infection.\n3. 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).\n4. Both community and hospital-acquired bacteremias will be included.\n5. 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.\n\nExclusion Criteria:\n\n1. More than 72 hr. elapsed since initial blood culture taken, regardless of the time covering antibiotics were started (up to 72 hrs.).\n2. 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.\n3. Patients with prior bacteremia or infection that have not completed antimicrobial therapy for the previous infectious episode.\n4. 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.\n5. BSI due to specific infections known at the time of randomization:\n\n 1. Endocarditis / endovascular infections\n 2. Osteomyelitis (not resected)\n 3. Central nervous system infections\n6. Allergy to any of the study drugs confirmed by history taken by the investigator\n7. Previous enrollment in this trial\n8. Concurrent participation in another interventional clinical trial\n9. Imminent death (researcher's assessment of expected death within 48 hrs. of recruitment)"}, 'identificationModule': {'nctId': 'NCT03671967', 'acronym': 'PETERPEN', 'briefTitle': 'PipEracillin Tazobactam Versus mERoPENem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae (PETERPEN)', 'organization': {'class': 'OTHER', 'fullName': 'Rambam Health Care Campus'}, 'officialTitle': 'Piperacillin Tazobactam Versus Meropenem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae- a Non-inferiority Randomized Controlled Trial', 'orgStudyIdInfo': {'id': 'MOH_2018-12-25_004857'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'piperacillin tazobactam', 'interventionNames': ['Drug: Piperacillin/tazobactam']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'meropenem', 'interventionNames': ['Drug: Meropenem']}], 'interventions': [{'name': 'Piperacillin/tazobactam', 'type': 'DRUG', 'description': '4.5 grams QID', 'armGroupLabels': ['piperacillin tazobactam']}, {'name': 'Meropenem', 'type': 'DRUG', 'description': '1 gram TID', 'armGroupLabels': ['meropenem']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'T2N 4Z6', 'city': 'Calgary', 'state': 'Alberta', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'John Conly, MD', 'role': 'CONTACT', 'email': 'jconly@ucalgary.ca'}, {'name': 'John Conly, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': "University of Calgary, Cumming School of Medicine, O'Brien Institute for Public Health", 'geoPoint': {'lat': 51.05011, 'lon': -114.08529}}, {'city': 'Surrey', 'state': 'British Columbia', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Kevin Afra, MD', 'role': 'CONTACT', 'email': 'Kevin.Afra@fraserhealth.ca'}, {'name': 'Kevin Afra, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Surrey Memorial Hospital - Fraser Health Authority', 'geoPoint': {'lat': 49.10635, 'lon': -122.82509}}, {'city': "St. John's", 'state': 'Newfoundland and Labrador', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Peter Daley, MD', 'role': 'CONTACT', 'email': 'pkd336@mun.ca'}, {'name': 'Peter Daley, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Eastern Health', 'geoPoint': {'lat': 47.56494, 'lon': -52.70931}}, {'city': 'Kingston', 'state': 'Ontario', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Tony Bai, MD', 'role': 'CONTACT', 'email': 'tony.bai@queensu.ca'}, {'name': 'Barbara Antuna Puente, MD', 'role': 'CONTACT', 'email': 'Barbarbara.antunapuente@queensu.ca'}], 'facility': 'Kingston General Hospital', 'geoPoint': {'lat': 44.22976, 'lon': -76.48098}}, {'zip': 'H3T 1E2', 'city': 'Montreal', 'state': 'Quebec', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Leighanne Parkes, MD', 'role': 'CONTACT'}, {'name': 'Leighanne Parkes', 'role': 'CONTACT', 'email': 'leighanne.parkes@mcgill.ca'}], 'facility': 'Jewish Genral Hospital', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}, {'city': 'Montreal, Quebec', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Todd Lee, MD', 'role': 'CONTACT'}, {'role': 'CONTACT', 'email': 'todd.lee@mcgill.ca'}, {'name': 'Todd Lee, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'McGill University Health Centre'}, {'zip': '3435306', 'city': 'Haifa', 'state': 'Israel', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Roni Bitterman', 'role': 'CONTACT', 'email': 'ro_oren@rambam.health.gov.il', 'phone': '47772991'}], 'facility': 'Rambam Health Care Campus', 'geoPoint': {'lat': 32.81303, 'lon': 34.99928}}, {'city': 'Beersheba', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Lior Nesher, MD', 'role': 'CONTACT', 'email': 'nesherke@bgu.ac.il'}, {'name': 'Lior Nesher', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Soroka Medical Center', 'geoPoint': {'lat': 31.25181, 'lon': 34.7913}}, {'city': 'Jerusalem', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Jacob strahilevitz, MD', 'role': 'CONTACT', 'email': 'jstrahilevitz@hadassah.org.il'}, {'name': 'Jacob strahilevitz, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Hadassah Medical Center', 'geoPoint': {'lat': 31.76904, 'lon': 35.21633}}, {'city': 'Kfar Saba', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Michal Chowers, MD', 'role': 'CONTACT', 'email': 'michalch@clalit.org.il'}, {'name': 'Michal Chowers, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Meir Medical Center', 'geoPoint': {'lat': 32.175, 'lon': 34.90694}}, {'zip': '42150', 'city': 'Netanya', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Candice Datnow, MD', 'role': 'CONTACT', 'email': 'cdatnow@laniado.org.il'}, {'name': 'Candice Datnow, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Sanz Medical Center-Laniado Hospital', 'geoPoint': {'lat': 32.33291, 'lon': 34.85992}}, {'city': 'Petah Tikva', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Alaa Atamna, MD', 'role': 'CONTACT', 'email': 'a.atamna86@gmail.com'}, {'name': 'Alaa Atamna, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Noa Eliakim-Raz, MD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Rabin Medical Center, Beilinson Campus', 'geoPoint': {'lat': 32.08707, 'lon': 34.88747}}, {'city': 'Tel Aviv', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Dafna Yahav, MD', 'role': 'CONTACT', 'email': 'dafna.yahav@gmail.com'}, {'name': 'Dafna Yahav, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Sheba Medical Center (Tel HaShomer)', 'geoPoint': {'lat': 32.08088, 'lon': 34.78057}}, {'city': 'Tel Aviv', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Ronen Ben-Ami, MD', 'role': 'CONTACT', 'email': 'ronenba@tlvmc.gov.il'}, {'name': 'Ronen Ben-Ami, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Sourasky Medical Center', 'geoPoint': {'lat': 32.08088, 'lon': 34.78057}}], 'centralContacts': [{'name': 'Mical Paul, MD', 'role': 'CONTACT', 'email': 'm_paul@rambam.health.gov.il', 'phone': '972-4-7772991'}, {'name': 'Roni Bitterman, MD', 'role': 'CONTACT', 'email': 'ro_oren@rambam.health.gov.il', 'phone': '972-4-7772991'}], 'overallOfficials': [{'name': 'Roni Bitterman, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Rambam Health Care Campus'}, {'name': 'Mical Paul, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Rambam Health Care Campus'}, {'name': 'Leonard Leibovici, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Rabin Medical Center'}, {'name': 'Cristina Mussini, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'University of Modena and Reggio Emilia'}, {'name': 'Noa Eliakim-Raz, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Rabin Medical Center, Beilinson Campus'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF', 'CSR', 'ANALYTIC_CODE'], 'timeFrame': 'following publication and for unlimited time', 'ipdSharing': 'YES', 'description': "De-identified individual patient data collected during the trial will be made available for an unlimited time period following publication of trial results. Data will be available for researchers who provide a methodologically sound proposal and contingent on both the researchers' and our ethics committee approval and the signing of a data sharing agreement.", 'accessCriteria': 'proposals should be sent to the principal investigator at ro\\_oren@rambam.health.gov.il'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Rambam Health Care Campus', 'class': 'OTHER'}, 'collaborators': [{'name': 'Rabin Medical Center', 'class': 'OTHER'}, {'name': 'University of Modena and Reggio Emilia', 'class': 'OTHER'}, {'name': 'Tel Aviv Medical Center', 'class': 'OTHER'}, {'name': 'Meir Medical Center', 'class': 'OTHER'}, {'name': 'Soroka University Medical Center', 'class': 'OTHER'}, {'name': 'The Chaim Sheba Medical Center', 'class': 'OTHER'}, {'name': 'McGill University Health Centre/Research Institute of the McGill University Health Centre', 'class': 'OTHER'}, {'name': 'Jewish General Hospital', 'class': 'OTHER'}, {'name': 'Canadian Institutes of Health Research (CIHR)', 'class': 'OTHER_GOV'}, {'name': 'Hadassah Medical Organization', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}