Bolus Versus Continuous Infusion of Meropenem

NCT ID: NCT03452839

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 607 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-05
• Study Completion Date: 2022-12-01

Brief 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.

Conditions

Antibiotic Resistant Infection; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Continuous infusion

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

1. for ClCr > 50 ml/min: 3 g / day, prepared as follows: 10 mg/ml of meropenem in NaCl 0.9% at 12,5 ml/h.

2. for ClCr < 50 ml/min: 2 g / day, prepared as follows: 10 mg/ml of meropenem in NaCl 0.9% at 8,3 ml/h.

This solution will be replaced every time its duration exceeds the stability in use stated by the producer

Group Type: EXPERIMENTAL

Meropenem

Intervention Type: DRUG

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

Bolus

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):

1. for Cl-Cr > 50 ml/min 1 g every 6 hours on first 24 hours, every 8 hours after

2. for Cl-Cr < 50 ml/min 1 g every 8 hours on first 24 hours, every 12 hours after

Group Type: ACTIVE_COMPARATOR

Meropenem

Intervention Type: DRUG

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

Interventions

Meropenem

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

Intervention Type: DRUG

Eligibility Criteria

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 β-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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università Vita-Salute San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Landoni

MD, Full Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alberto Zangrillo, Prof

Role: PRINCIPAL_INVESTIGATOR

IRCCS San Raffaele Scientific Institute

Giacomo Monti, MD

Role: STUDY_CHAIR

IRCCS San Raffaele Scientific Institute

Locations

University Hospital Dubrava

Dubrava, , Croatia

Città di Lecce Hospital

Lecce, Apulia, Italy

ASST Cremona

Cremona, Cemona, Italy

Policlinico Univeristario Campus Bio-Medico

Rome, Lazio, Italy

Ospedale San Raffaele di Milano

Milan, MI, 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

Napoli, , Italy

Azienda Ospedale - Università Padova - Ospedale "Sant'Antonio

Padua, , 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

Countries

Croatia; Italy; Kazakhstan; Russia

References

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.

Reference Type: BACKGROUND

PMID: 33684595 (View on PubMed)

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.

Reference Type: RESULT

PMID: 37326473 (View on PubMed)

Other Identifiers

2016-002052-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MERCY/9A/OSR

Identifier Type: -

Identifier Source: org_study_id