Bolus Versus Continuous Infusion of Meropenem

Critical Illness Clinical Trial

— MERCY  

Official title:

Continuous Infusion Versus Intermittent Administration of Meropenem in Critically Ill Patients: A Multicenter Randomized Double Blind Trial

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
• 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
• 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)

Related Conditions & MeSH terms

• Antibiotic Resistant Infection
• Critical Illness

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