Antibiotic Resistant InfectionPhase 4MERCYNCT03452839
Bolus Versus Continuous Infusion of Meropenem
A Phase 4 study testing Meropenem in people with Antibiotic Resistant Infection and Critical Illness, run by Università Vita-Salute San Raffaele at 26 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antibiotic Resistant Infection, Critical Illness
- What is being tested?
- Meropenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 607 participants
- Where
- 26 sitesin 4 countries
- Study dates
- 5 Jun 2018to 1 Dec 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
26 sites in 4 countries.
26 sites in 4 countries
Italy22 sites
Ospedale San Lazzaro ASL CN2
Alba
Azienda Ospedaliera Universitaria
Cagliari, Sardinia
Ospedale A. Cardarelli
Campobasso
P.O. Pineta Grande - Castelvolturno
Caserta
A.O.U. Mater Domini
Catanzaro, Reggio Calabria
ASST Cremona
Cremona, Cemona
Azienda Ospedaliero Universitaria Careggi - Firenze
Florence
Azienda Universitario-Ospedaliera O.O.R.R.
Foggia
E. O. Ospedali Galliera
Genova
Città di Lecce Hospital
Lecce, Apulia
Ospedale di Merano
Merano
Ospedale San Raffaele di Milano
Milan, MI, 20132
Università degli Studi della Campania "L. Vanvitelli
Naples
Azienda Ospedale - Università Padova - Ospedale "Sant'Antonio
Padova
AOU Pisana
Pisa
A.O.R San Carlo
Potenza
Grande Ospedale Metropolitano
Reggio Calabria
Policlinico Univeristario Campus Bio-Medico
Rome, Lazio
Humanitas Research Hospital
Rozzano
USSL 10 Veneto
San Donà di Piave, Venezia
AO Città della Salute e della Scienza
Torino
Università di Udine
Udine
Russia2 sites
Federal Clinical & Research Center for Reanimatology and Rehabilitation
Moscow
I.M. Sechenov Firts Moscow State Medical
Moscow
About this study
Official title: Continuous Infusion Versus Intermittent Administration of Meropenem in Critically Ill Patients: A Multicenter Randomized Double Blind Trial
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
- Being tested
- Meropenem
- Keywords
- meropenem, antibiotic resistance, critical illness, β-lactams, continuous antibacterial drug infusion, mortality
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MeropenemDrug
Meropenem or injection vials to be re-constituted in a solution of NaCl 0.9%.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Meropenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: day 28
Secondary outcomes (4)
Death from any cause
Death from any cause
Measured: day 90
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)
Measured: up to day 28 or death
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
Measured: day 28 or death
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.
Measured: up to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2018
- Study start5 Jun 2018
- Primary completion1 Oct 2022
- Study completion1 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Antibiotic Resistant InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 607 participants (actual)
Sponsor and investigators
- Lead sponsor
- Università Vita-Salute San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Landoni, Università Vita-Salute San Raffaele
- Investigators
- Alberto Zangrillo, Prof, Principal investigator, IRCCS San Raffaele Scientific InstituteGiacomo Monti, MD, Study chair, IRCCS San Raffaele Scientific Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03452839
- Sponsor's protocol ID
- MERCY/9A/OSR
- Other IDs
- 2016-002052-24, 2016
- Acronym
- MERCY
- Status last verified
- Aug 2025
- First submitted
- 26 Feb 2018
- Last updated
- 6 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33684595Monti 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.
PubMed 37326473
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Continuous Infusion Versus Intermittent Administration of Meropenem in Critically Ill Patients: A Multicenter Randomized Double Blind Trial
- ClinicalTrials.gov ID
- NCT03452839
- Acronym / sponsor ID
- MERCY / MERCY/9A/OSR
- Conditions
- Antibiotic Resistant Infection, Critical Illness
- Keywords
- meropenem, antibiotic resistance, critical illness, β-lactams, continuous antibacterial drug infusion, mortality
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 607 participants (actual)
- Lead sponsor
- Università Vita-Salute San RaffaeleUniversity, hospital or other
- Study start
- 5 Jun 2018 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 1 Dec 2022 (actual)
- First posted
- 2 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous infusion | Experimental | Drug: MeropenemPatient 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 |
| Bolus | Active comparator | Drug: MeropenemPatient 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MeropenemMeropenem or injection vials to be re-constituted in a solution of NaCl 0.9%. | Drug | Bolus, Continuous infusion |
Primary outcome
Death or Emergence of new resistant bacteria
Time frame: day 28
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
4 secondary outcomes
Death from any cause
Time frame: day 90
Antibiotic-free days
Time frame: up to day 28 or death
ICU - free days
Time frame: day 28 or death
Cumulative SOFA-free point
Time frame: up to day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2025.
- Background: PubMed 33684595Monti 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 publication: PubMed 37326473Monti 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alberto Zangrillo, Prof principal investigator
IRCCS San Raffaele Scientific Institute
Giacomo Monti, MD study chair
IRCCS San Raffaele Scientific Institute
26 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Meropenem in people with Antibiotic Resistant Infection and Critical Illness, run by Università Vita-Salute San Raffaele at 26 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Italy, Russia, Croatia, Kazakhstan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Death or Emergence of new resistant bacteria (time frame: day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03452839, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2025.