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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002052-24 | EudraCT Number |
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This study arises from the need to optimize antibacterial drug usage to face increasing drug resistance among gram-negative pathogens in intensive care units. Gram-negative organisms are responsible for 70% of drug-resistant infections acquired in the intensive care unit. Meropenem is a β-lactam, carbapenem, antibacterial agent usually administered by intermittent infusion. As β-lactam efficacy is determined by the time in which the drug concentration exceeds the minimum inhibiting concentration of the target pathogen, intermittent infusion of this short half-lived drug can lead to precipitous drops in serum drug levels, an occurrence linked to emergence of resistant pathogens. The investigators hypothesize a beneficial effect of a continuous meropenem infusion on mortality and emergence of drug resistant pathogens. All patients enrolled will receive 1 g of meropenem bolus. After that, subjects will be randomized to receive a continuous infusion of study drug 3g/day or a bolus administration of the same amount of drugs. The investigators expect a reduction of mortality and emergence of extensive or pan drug resistant pathogens from 52 to 40% in the continuous infusion group.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Continuous infusion | Experimental | Patient randomized to continuous infusion group, will receive a continuous infusion of meropenem according to their renal function (creatinine clearance -ClCr- estimated by Cockcroft-Gault formula and study day
This solution will be replaced every time its duration exceeds the stability in use stated by the producer |
|
| Bolus | Active Comparator | Patient randomized to bolus group, will receive a bolus infusion of meropenem according to their renal function (creatinine clearance -ClCr- estimated by Cockcroft-Gault formula):
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Meropenem | Drug | Meropenem or injection vials to be re-constituted in a solution of NaCl 0.9%. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Death or Emergence of new resistant bacteria | composite outcome:
| day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Death from any cause | Death from any cause | day 90 |
| Antibiotic-free days | Proportion of days from randomization to day 28 or death in which subject didn't receive any antibiotics (excluding anti-fungal anti-viral drugs) |
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Inclusion Criteria:
Will be enrolled patients who:
Exclusion Criteria:
Will be excluded patients who:
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| Name | Affiliation | Role |
|---|---|---|
| Alberto Zangrillo, Prof | IRCCS San Raffaele Scientific Institute | Principal Investigator |
| Giacomo Monti, MD | IRCCS San Raffaele Scientific Institute | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Dubrava | Dubrava | Croatia | ||||
| Città di Lecce Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33684595 | Background | Monti G, Galbiati C, Toffoletto F, Calabro MG, Colombo S, Ferrara B, Giardina G, Lembo R, Marzaroli M, Moizo E, Mucci M, Pasculli N, Plumari VP, Scandroglio AM, Tozzi M, Momesso E, Boffa N, Lobreglio R, Montrucchio G, Guarracino F, Benedetto U, Biondi-Zoccai G, D'Ascenzo F, D'Andrea N, Paternoster G, Ananiadou S, Ballestra M, De Sio A, Pota V, Cotoia A, Della Selva A, Bruni A, Iapichino G, Bradic N, Corradi F, Gemma M, Nogtev P, Petrova M, Agro FE, Cabrini L, Forfori F, Likhvantsev V, Bove T, Finco G, Landoni G, Zangrillo A; Collaborators. Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design. Contemp Clin Trials. 2021 May;104:106346. doi: 10.1016/j.cct.2021.106346. Epub 2021 Mar 6. | |
| 37326473 |
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| up to day 28 or death |
| ICU - free days | Number of days from randomization to day 28 (or death) in which the subject is outside the ICU. For any discharge lasting less than 48h, no ICU-free day will be computed. Re-admission lasting less than 24 hours will not reduce ICU-free days. Patients that will not survive outside ICU for at least 48 hours, will have a ICU-free day of zero | day 28 or death |
| Cumulative SOFA-free point | SOFA score will be evaluated every day up to day 28. SOFA-free daily score is 24 (maximum SOFA) minus actual SOFA. Cumulative SOFA-free is the sum of SOFA-free daily from randomization to date 28. Patients dead before day 28 can't ameliorate their SOFA-free score. This way, the higher the cumulative SOFA-free, the higher is the amelioration of the patient and his probability of survival. | up to day 28 |
| Lecce |
| Apulia |
| Italy |
| ASST Cremona | Cremona | Cemona | Italy |
| Policlinico Univeristario Campus Bio-Medico | Rome | Lazio | Italy |
| Ospedale San Raffaele di Milano | Milan | MI | 20132 | Italy |
| A.O.U. Mater Domini | Catanzaro | Reggio Calabria | Italy |
| Azienda Ospedaliera Universitaria | Cagliari | Sardinia | Italy |
| USSL 10 Veneto | San Donà di Piave | Venezia | Italy |
| Ospedale San Lazzaro ASL CN2 | Alba | Italy |
| Ospedale A. Cardarelli | Campobasso | Italy |
| P.O. Pineta Grande - Castelvolturno | Caserta | Italy |
| Azienda Ospedaliero Universitaria Careggi - Firenze | Florence | Italy |
| Azienda Universitario-Ospedaliera O.O.R.R. | Foggia | Italy |
| E. O. Ospedali Galliera | Genova | Italy |
| Ospedale di Merano | Merano | Italy |
| Università degli Studi della Campania "L. Vanvitelli | Naples | Italy |
| Azienda Ospedale - Università Padova - Ospedale "Sant'Antonio | Padova | Italy |
| AOU Pisana | Pisa | Italy |
| A.O.R San Carlo | Potenza | Italy |
| Grande Ospedale Metropolitano | Reggio Calabria | Italy |
| Humanitas Research Hospital | Rozzano | Italy |
| AO Città della Salute e della Scienza | Torino | Italy |
| Università di Udine | Udine | Italy |
| Astana Medical University | Kazakhstan | Kazakhstan |
| Federal Clinical & Research Center for Reanimatology and Rehabilitation | Moscow | Russia |
| I.M. Sechenov Firts Moscow State Medical | Moscow | Russia |
| Result |
| Monti G, Bradic N, Marzaroli M, Konkayev A, Fominskiy E, Kotani Y, Likhvantsev VV, Momesso E, Nogtev P, Lobreglio R, Redkin I, Toffoletto F, Bruni A, Baiardo Redaelli M, D'Andrea N, Paternoster G, Scandroglio AM, Gallicchio F, Ballestra M, Calabro MG, Cotoia A, Perone R, Cuffaro R, Montrucchio G, Pota V, Ananiadou S, Lembo R, Musu M, Rauch S, Galbiati C, Pinelli F, Pasin L, Guarracino F, Santarpino G, Agro FE, Bove T, Corradi F, Forfori F, Longhini F, Cecconi M, Landoni G, Bellomo R, Zangrillo A; MERCY Investigators. Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial. JAMA. 2023 Jul 11;330(2):141-151. doi: 10.1001/jama.2023.10598. |
| ID | Term |
|---|---|
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077731 | Meropenem |
| ID | Term |
|---|---|
| D013845 | Thienamycins |
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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