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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03452839
Other study ID # MERCY/9A/OSR
Secondary ID 2016-002052-24
Status Completed
Phase Phase 4
First received
Last updated
Start date June 5, 2018
Est. completion date December 1, 2022

Study information

Verified date December 2022
Source Università Vita-Salute San Raffaele
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Completed
Enrollment 607
Est. completion date December 1, 2022
Est. primary completion date October 1, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: Will be enrolled patients who: - Are able to express informed consent or the latter can be given by his/her next of kin or as requested by Ethical Committee. - Need a new antibiotic treatment, by clinical judgment, with meropenem - Are admitted to ICU - Have Sepsis or septic shock. Sepsis defined as having all the following 1. SIRS (Systemic Inflammatory Response Syndrome); 2. suspected or documented infection; 3. a SOFA score = 2. Septic shock defined as having all the following 1.Sepsis; 2. Persisting hypotension requiring vasopressors to maintain MAP =65mmHg and having a serum lactate level >2 mmol/L (18mg/dL) despite adequate volume resuscitation. Exclusion Criteria: Will be excluded patients who: - Are able to express informed consent and deny it - Are already receiving study drug or other carbapenem both as a bolus or continuous infusion - Have a known allergy or intolerance to study drug, to other carbapenem antibacterial agents or severe allergic reaction to ß-lactam antibacterial agents or to anhydrous sodium carbonate (study drug excipient) - Have a little chance of survival, as defined by a SAPS II score greater than 65 - Have concomitant acquired immunodeficiency syndrome (stage 3 according to CDC) - Received immunosuppressant or long-term corticosteroid therapy (more than 0.5 mg/kg/day for over 30 days)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Meropenem
Meropenem or injection vials to be re-constituted in a solution of NaCl 0.9%.

Locations

Country Name City State
Croatia University Hospital Dubrava Dubrava
Italy Ospedale San Lazzaro ASL CN2 Alba
Italy Azienda Ospedaliera Universitaria Cagliari Sardegna
Italy Ospedale A. Cardarelli Campobasso
Italy P.O. Pineta Grande - Castelvolturno Caserta
Italy A.O.U. Mater Domini Catanzaro Reggio Calabria
Italy ASST Cremona Cremona Cemona
Italy Azienda Ospedaliero Universitaria Careggi - Firenze Firenze
Italy Azienda Universitario-Ospedaliera O.O.R.R. Foggia
Italy E. O. Ospedali Galliera Genova
Italy Città di Lecce Hospital Lecce Puglia
Italy Ospedale di Merano Merano
Italy Ospedale San Raffaele di Milano Milan MI
Italy Università degli Studi della Campania "L. Vanvitelli Napoli
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 Policlinico Univeristario Campus Bio-Medico Roma Lazio
Italy Humanitas Research Hospital Rozzano
Italy USSL 10 Veneto San Dona' Di Piave Venezia
Italy AO Città della Salute e della Scienza Torino
Italy Università di Udine Udine
Kazakhstan Astana Medical University Kazakhstan
Russian Federation Federal Clinical & Research Center for Reanimatology and Rehabilitation Moscow
Russian Federation I.M. Sechenov Firts Moscow State Medical Moscow

Sponsors (1)

Lead Sponsor Collaborator
Università Vita-Salute San Raffaele

Countries where clinical trial is conducted

Croatia,  Italy,  Kazakhstan,  Russian Federation, 

References & Publications (1)

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Death or Emergence of new resistant bacteria composite outcome:
death from any cause at day 28
emergence of new XDR (extended drug resistant) or PDR (pan drug resistant) bacteria at day 28
day 28
Secondary Death from any cause Death from any cause day 90
Secondary 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) up to day 28 or death
Secondary 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
Secondary 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
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