search
Back to results

Bolus Versus Continuous Infusion of Meropenem (MERCY)

Primary Purpose

Antibiotic Resistant Infection, Critical Illness

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Meropenem
Sponsored by
Università Vita-Salute San Raffaele
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Antibiotic Resistant Infection focused on measuring meropenem, antibiotic resistance, critical illness, β-lactams, continuous antibacterial drug infusion, mortality

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University Hospital Dubrava
  • ASST Cremona
  • Policlinico Univeristario Campus Bio-Medico
  • Ospedale San Raffaele di Milano
  • Città di Lecce Hospital
  • A.O.U. Mater Domini
  • Azienda Ospedaliera Universitaria
  • USSL 10 Veneto
  • Ospedale San Lazzaro ASL CN2
  • Ospedale A. Cardarelli
  • P.O. Pineta Grande - Castelvolturno
  • Azienda Ospedaliero Universitaria Careggi - Firenze
  • Azienda Universitario-Ospedaliera O.O.R.R.
  • E. O. Ospedali Galliera
  • Ospedale di Merano
  • Università degli Studi della Campania "L. Vanvitelli
  • Azienda Ospedale - Università Padova - Ospedale "Sant'Antonio
  • AOU Pisana
  • A.O.R San Carlo
  • Grande Ospedale Metropolitano
  • Humanitas Research Hospital
  • AO Città della Salute e della Scienza
  • Università di Udine
  • Astana Medical University
  • Federal Clinical & Research Center for Reanimatology and Rehabilitation
  • I.M. Sechenov Firts Moscow State Medical

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Continuous infusion

Bolus

Arm Description

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 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. 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

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): for Cl-Cr > 50 ml/min 1 g every 6 hours on first 24 hours, every 8 hours after for Cl-Cr < 50 ml/min 1 g every 8 hours on first 24 hours, every 12 hours after

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Death from any cause
Death from any cause
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)
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
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.

Full Information

First Posted
February 26, 2018
Last Updated
December 23, 2022
Sponsor
Università Vita-Salute San Raffaele
search

1. Study Identification

Unique Protocol Identification Number
NCT03452839
Brief Title
Bolus Versus Continuous Infusion of Meropenem
Acronym
MERCY
Official Title
Continuous Infusion Versus Intermittent Administration of Meropenem in Critically Ill Patients: A Multicenter Randomized Double Blind Trial
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
June 5, 2018 (Actual)
Primary Completion Date
October 1, 2022 (Actual)
Study Completion Date
December 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Università Vita-Salute San Raffaele

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Antibiotic Resistant Infection, Critical Illness
Keywords
meropenem, antibiotic resistance, critical illness, β-lactams, continuous antibacterial drug infusion, mortality

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
607 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Continuous infusion
Arm Type
Experimental
Arm Description
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 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. 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
Arm Title
Bolus
Arm Type
Active Comparator
Arm Description
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): for Cl-Cr > 50 ml/min 1 g every 6 hours on first 24 hours, every 8 hours after for Cl-Cr < 50 ml/min 1 g every 8 hours on first 24 hours, every 12 hours after
Intervention Type
Drug
Intervention Name(s)
Meropenem
Intervention Description
Meropenem or injection vials to be re-constituted in a solution of NaCl 0.9%.
Primary Outcome Measure Information:
Title
Death or Emergence of new resistant bacteria
Description
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
Time Frame
day 28
Secondary Outcome Measure Information:
Title
Death from any cause
Description
Death from any cause
Time Frame
day 90
Title
Antibiotic-free days
Description
Proportion of days from randomization to day 28 or death in which subject didn't receive any antibiotics (excluding anti-fungal anti-viral drugs)
Time Frame
up to day 28 or death
Title
ICU - free days
Description
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
Time Frame
day 28 or death
Title
Cumulative SOFA-free point
Description
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.
Time Frame
up to day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alberto Zangrillo, Prof
Organizational Affiliation
IRCCS San Raffaele Scientific Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Giacomo Monti, MD
Organizational Affiliation
IRCCS San Raffaele Scientific Institute
Official's Role
Study Chair
Facility Information:
Facility Name
University Hospital Dubrava
City
Dubrava
Country
Croatia
Facility Name
ASST Cremona
City
Cremona
State/Province
Cemona
Country
Italy
Facility Name
Policlinico Univeristario Campus Bio-Medico
City
Roma
State/Province
Lazio
Country
Italy
Facility Name
Ospedale San Raffaele di Milano
City
Milan
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Facility Name
Città di Lecce Hospital
City
Lecce
State/Province
Puglia
Country
Italy
Facility Name
A.O.U. Mater Domini
City
Catanzaro
State/Province
Reggio Calabria
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria
City
Cagliari
State/Province
Sardegna
Country
Italy
Facility Name
USSL 10 Veneto
City
San Dona' Di Piave
State/Province
Venezia
Country
Italy
Facility Name
Ospedale San Lazzaro ASL CN2
City
Alba
Country
Italy
Facility Name
Ospedale A. Cardarelli
City
Campobasso
Country
Italy
Facility Name
P.O. Pineta Grande - Castelvolturno
City
Caserta
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria Careggi - Firenze
City
Firenze
Country
Italy
Facility Name
Azienda Universitario-Ospedaliera O.O.R.R.
City
Foggia
Country
Italy
Facility Name
E. O. Ospedali Galliera
City
Genova
Country
Italy
Facility Name
Ospedale di Merano
City
Merano
Country
Italy
Facility Name
Università degli Studi della Campania "L. Vanvitelli
City
Napoli
Country
Italy
Facility Name
Azienda Ospedale - Università Padova - Ospedale "Sant'Antonio
City
Padova
Country
Italy
Facility Name
AOU Pisana
City
Pisa
Country
Italy
Facility Name
A.O.R San Carlo
City
Potenza
Country
Italy
Facility Name
Grande Ospedale Metropolitano
City
Reggio Calabria
Country
Italy
Facility Name
Humanitas Research Hospital
City
Rozzano
Country
Italy
Facility Name
AO Città della Salute e della Scienza
City
Torino
Country
Italy
Facility Name
Università di Udine
City
Udine
Country
Italy
Facility Name
Astana Medical University
City
Kazakhstan
Country
Kazakhstan
Facility Name
Federal Clinical & Research Center for Reanimatology and Rehabilitation
City
Moscow
Country
Russian Federation
Facility Name
I.M. Sechenov Firts Moscow State Medical
City
Moscow
Country
Russian Federation

12. IPD Sharing Statement

Citations:
PubMed Identifier
33684595
Citation
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.
Results Reference
background

Learn more about this trial

Bolus Versus Continuous Infusion of Meropenem

We'll reach out to this number within 24 hrs