Ignite Creation Date:
2025-12-24 @ 4:50 PM
Ignite Modification Date:
2026-01-06 @ 5:10 AM
Study NCT ID:
NCT05355350
Status:
WITHDRAWN
Last Update Posted:
2025-07-24
First Post:
2022-04-04
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PipEracillin/Tazobactam Versus mERoPENem for Treatment of AmpC Producing Blood Stream Infections
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'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'No eligible patients', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2022-07-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2025-07-21', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-07-21', 'studyFirstSubmitDate': '2022-04-04', 'studyFirstSubmitQcDate': '2022-04-29', 'lastUpdatePostDateStruct': {'date': '2025-07-24', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-05-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-07-21', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'All-cause mortality', 'timeFrame': '30 days from randomization', 'description': 'Primary Outcome Measure'}, {'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]', 'description': 'Number of deceased patients'}, {'measure': 'Number of participants with 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': 'Number of participants with 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': 'Number of participants with 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': 'Number of participants with Clostridium difficile associated diarrhea', 'timeFrame': '90 days from randomization', 'description': 'Diarrhea with positive Clostridium difficile toxin test'}, {'measure': 'Secondary bacterial infections', 'timeFrame': '90 days from randomization', 'description': 'Number of participants with a new clinically-significant infection, with or without microbiological documentation. Defined using NHSN criteria for healthcare-associated infections.'}, {'measure': 'Number of participants with hospital re-admissions', 'timeFrame': '90 days from randomization', 'description': 'Hospital re-admission, excluding index hospitalization'}, {'measure': 'Number of participants with development of antimicrobial 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 detected by weekly rectal surveillance of carriage while in-hospital', 'timeFrame': '90 days from randomization', 'description': 'New acquisition of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE carbapenem-resistant Enterobacteriaceae, detected through rectal surveillance or clinical cultures'}, {'measure': 'Total in-hospital days', 'timeFrame': '30 days and 90 days from randomization', 'description': 'Total of in-hospital days per participant, including all admissions'}, {'measure': 'Total antibiotic days', 'timeFrame': '30 days and 90 days from randomization', 'description': 'Total antibiotic days per participant within all admissions'}, {'measure': 'Adverse events', 'timeFrame': '30 days', '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']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': 'PeterPen-SPICE-M will expland the PeterPen trial. In PeterPen we recruit patients with bacteremia caused by 3rd generation cephalosporin-resistant E. coli or Klebsiella pneumoniae. In SPICE-M we will recruit also patients with bacteremia caused by 3rd generation cephalosporin-resistant Serratia marcescens, Providencia stuartii \\& rettgeri, Indole positive Proteus spp. (Proteus vulgaris), Citrobacter freundii, Enterobacter cloacae, Klebsiella aerogenes and Morganella morganii. In both trials patients will be allocated within 72 hours of blood culture taking to piperacillin-tazobactam vs. meropenem to complete at least 7 days of covering antibiotic therapy.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '120 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Adults (age ≥ 18 years)\n2. 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.\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 study pathogens 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) or patient in palliative care"}, 'identificationModule': {'nctId': 'NCT05355350', 'acronym': 'SPICE-M', 'briefTitle': 'PipEracillin/Tazobactam Versus mERoPENem for Treatment of AmpC Producing Blood Stream Infections', 'organization': {'class': 'OTHER', 'fullName': 'Rambam Health Care Campus'}, 'officialTitle': 'PipEracillin/Tazobactam vs mERoPENem for Treatment of AmpC-producing Bloodstream Infections: an Extension of the Original PETERPEN Trial', 'orgStudyIdInfo': {'id': '0295-18-RMB'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'piperacillin tazobactam', 'interventionNames': ['Drug: Piperacillin / Tazobactam Injection']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'meropenem', 'interventionNames': ['Drug: Meropenem']}], 'interventions': [{'name': 'Piperacillin / Tazobactam Injection', 'type': 'DRUG', 'description': '4.5 grams QID', 'armGroupLabels': ['piperacillin tazobactam']}, {'name': 'Meropenem', 'type': 'DRUG', 'description': '1 gram TID', 'armGroupLabels': ['meropenem']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Haifa', 'country': 'Israel', 'facility': 'Rambam Health Care Campus', 'geoPoint': {'lat': 32.81303, 'lon': 34.99928}}, {'city': 'Jerusalem', 'country': 'Israel', 'facility': 'Hadassah Medical Center', 'geoPoint': {'lat': 31.76904, 'lon': 35.21633}}, {'city': 'Petah Tikva', 'country': 'Israel', 'facility': 'Rabin Medical Center, Beilinson Hospital', 'geoPoint': {'lat': 32.08707, 'lon': 34.88747}}, {'city': 'Ramat Gan', 'country': 'Israel', 'facility': 'Sheba Tel HaShomer Medical Campus', 'geoPoint': {'lat': 32.08227, 'lon': 34.81065}}], 'overallOfficials': [{'name': 'Mical Paul, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Rambam Health Care Campus'}, {'name': 'Dafna Yahav, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Sheba Tel HaShomer Medical Campus'}, {'name': 'Alaa Atamna, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Rabin Medical Center, Beilinson Campus'}, {'name': 'Roni Bitterman, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Rambam Health Care Campus'}, {'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 m\\_paul@rambam.health.gov.il'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Rambam Health Care Campus', 'class': 'OTHER'}, 'collaborators': [{'name': 'The Chaim Sheba Medical Center', 'class': 'OTHER'}, {'name': 'Rabin Medical Center', 'class': 'OTHER'}, {'name': 'Hadassah Medical Organization', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Prof. Mical Paul, MD', 'investigatorFullName': 'MICHAL PAUL md', 'investigatorAffiliation': 'Rambam Health Care Campus'}}}}