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| Name | Class |
|---|---|
| Rabin Medical Center | OTHER |
| University of Modena and Reggio Emilia | OTHER |
| Tel Aviv Medical Center | OTHER |
| Meir Medical Center |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| piperacillin tazobactam | Experimental |
| |
| meropenem | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Piperacillin/tazobactam | Drug | 4.5 grams QID |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause mortality | 14 and 90 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 |
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Inclusion Criteria:
Exclusion Criteria:
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:
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)
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| 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 |
| Name | Affiliation | Role |
|---|---|---|
| Roni Bitterman, MD | Rambam Health Care Campus | Principal Investigator |
| Mical Paul, MD | Rambam Health Care Campus | Study Director |
| Leonard Leibovici, MD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Calgary, Cumming School of Medicine, O'Brien Institute for Public Health | Recruiting | Calgary | Alberta | T2N 4Z6 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33558347 | Derived | 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. |
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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.
following publication and for unlimited time
proposals should be sent to the principal investigator at ro_oren@rambam.health.gov.il
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| OTHER |
| Soroka University Medical Center | OTHER |
| The Chaim Sheba Medical Center | OTHER |
| McGill University Health Centre/Research Institute of the McGill University Health Centre | OTHER |
| Jewish General Hospital | OTHER |
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
| Hadassah Medical Organization | OTHER |
open-label randomized controlled trial
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| Meropenem |
| Drug |
1 gram TID |
|
| 14 days and 30 days from randomization |
| Microbiological failure | Repeat positive blood cultures with index pathogen on day 4 or later from randomization | 7 days and 14 days from randomization |
| Recurrent positive blood cultures (relapse) | recurrent positive blood cultures with the index pathogen after prior sterilization of blood cultures or after end of treatment | 30 days and 90 days from randomization |
| Clostridium difficile associated diarrhea | 90 days from randomization |
| Clinically or microbiologically documented infection other than Gram-negative bacteremia | 90 days from randomization |
| Number of hospital re-admissions | 90 days from randomization |
| Development of resistance | clinical isolates resistant to piperacillin/tazobactam and meropenem and any carbapenem-resistant bacteria | 90 days from randomization |
| Carriage of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE carbapenem-resistant Enterobacteriaceae in-hospital | detected by weekly rectal surveillance of carriage while in-hospital | 90 days from randomization |
| Total in-hospital days | 30 days and 90 days from randomization |
| Total antibiotic days | 30 days and 90 days from randomization |
| Adverse events | diarrhea, liver function test abnormalities, antibiotic rash or other immediate-type allergy, acute kidney injury defined according to RIFLE criteria | 30 days from randomization |
| 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 |
| Surrey Memorial Hospital - Fraser Health Authority | Recruiting | Surrey | British Columbia | Canada |
|
| Eastern Health | Recruiting | St. John's | Newfoundland and Labrador | Canada |
|
| Kingston General Hospital | Recruiting | Kingston | Ontario | Canada |
|
| Jewish Genral Hospital | Recruiting | Montreal | Quebec | H3T 1E2 | Canada |
|
| McGill University Health Centre | Recruiting | Montreal, Quebec | Canada |
|
| Rambam Health Care Campus | Recruiting | Haifa | Israel | 3435306 | Israel |
|
| Soroka Medical Center | Recruiting | Beersheba | Israel |
|
| Hadassah Medical Center | Recruiting | Jerusalem | Israel |
|
| Meir Medical Center | Recruiting | Kfar Saba | Israel |
|
| Sanz Medical Center-Laniado Hospital | Recruiting | Netanya | 42150 | Israel |
|
| Rabin Medical Center, Beilinson Campus | Recruiting | Petah Tikva | Israel |
|
| Sheba Medical Center (Tel HaShomer) | Recruiting | Tel Aviv | Israel |
|
| Sourasky Medical Center | Recruiting | Tel Aviv | Israel |
|
| ID | Term |
|---|---|
| D004756 | Enterobacteriaceae Infections |
| D016470 | Bacteremia |
| ID | Term |
|---|---|
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D018805 | Sepsis |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077725 | Piperacillin, Tazobactam Drug Combination |
| D000077731 | Meropenem |
| ID | Term |
|---|---|
| D000078142 | Tazobactam |
| D010397 | Penicillanic Acid |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D010878 | Piperacillin |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D013457 | Sulfur Compounds |
| D013450 | Sulfones |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D013845 | Thienamycins |
| D015780 | Carbapenems |
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