Bolus Versus Continuous Infusion of Meropenem

NCT03452839 | Completed Phase 4

• 2 other identifiers: MERCY/9A/OSR2016-002052-24
• Study Type: interventional
• Target: 607
• Locations: 4 countries
• Sites: 26

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

Keywords

meropenem; antibiotic resistance; critical illness; β-lactams; continuous antibacterial drug infusion; mortality

Outcome Measures

Primary Outcomes (1)

• Death or Emergence of new resistant bacteria

  composite outcome: 1. death from any cause at day 28 2. emergence of new XDR (extended drug resistant) or PDR (pan drug resistant) bacteria at day 28

  day 28

Secondary Outcomes (4)

• Death from any cause

  day 90

• Antibiotic-free days

  up to day 28 or death

• ICU - free days

  day 28 or death

• Cumulative SOFA-free point

  up to day 28

Study Arms (2)

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 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

Drug: Meropenem

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): 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

Drug: Meropenem

Interventions

Meropenem DRUG

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

Bolus; Continuous infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead

Study Sites (26)

University Hospital Dubrava

Dubrava, Croatia

Location

Città di Lecce Hospital

Lecce, Apulia, Italy

Location

ASST Cremona

Cremona, Cemona, Italy

Location

Policlinico Univeristario Campus Bio-Medico

Rome, Lazio, Italy

Location

Ospedale San Raffaele di Milano

Milan, MI, 20132, Italy

Location

A.O.U. Mater Domini

Catanzaro, Reggio Calabria, Italy

Location

Azienda Ospedaliera Universitaria

Cagliari, Sardinia, Italy

Location

USSL 10 Veneto

San Donà di Piave, Venezia, Italy

Location

Ospedale San Lazzaro ASL CN2

Alba, Italy

Location

Ospedale A. Cardarelli

Campobasso, Italy

Location

P.O. Pineta Grande - Castelvolturno

Caserta, Italy

Location

Azienda Ospedaliero Universitaria Careggi - Firenze

Florence, Italy

Location

Azienda Universitario-Ospedaliera O.O.R.R.

Foggia, Italy

Location

E. O. Ospedali Galliera

Genova, Italy

Location

Ospedale di Merano

Merano, Italy

Location

Università degli Studi della Campania "L. Vanvitelli

Napoli, Italy

Location

Azienda Ospedale - Università Padova - Ospedale "Sant'Antonio

Padua, Italy

Location

AOU Pisana

Pisa, Italy

Location

A.O.R San Carlo

Potenza, Italy

Location

Grande Ospedale Metropolitano

Reggio Calabria, Italy

Location

Humanitas Research Hospital

Rozzano, Italy

Location

AO Città della Salute e della Scienza

Torino, Italy

Location

Università di Udine

Udine, Italy

Location

Astana Medical University

Kazakhstan, Kazakhstan

Location

Federal Clinical & Research Center for Reanimatology and Rehabilitation

Moscow, Russia

Location

I.M. Sechenov Firts Moscow State Medical

Moscow, Russia

Location

Related Publications (2)

• 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.

  PMID: 33684595 BACKGROUND

• 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.

  PMID: 37326473 RESULT

MeSH Terms

Conditions

Critical Illness

Interventions

Meropenem

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Alberto Zangrillo, Prof

  IRCCS San Raffaele Scientific Institute

  PRINCIPAL INVESTIGATOR

• Giacomo Monti, MD

  IRCCS San Raffaele Scientific Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Full Professor

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: March 2, 2018
• Study Start: June 5, 2018
• Primary Completion: October 1, 2022
• Study Completion: December 1, 2022
• Last Updated: August 6, 2025

Record last verified: 2025-08

Locations

CR (1); IT (22); KA (1); RU (2)