Bolus Versus Continuous Infusion of Meropenem (MERCY)

Università Vita-Salute San Raffaele

Status and phase: Completed; Phase 4

Conditions: Critical Illness; Antibiotic Resistant Infection

Treatments: Drug: Meropenem

Study type: Interventional

Funder types: Other

Identifiers

NCT03452839

2016-002052-24 (EudraCT Number)

MERCY/9A/OSR

Details and patient eligibility

About

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.

Enrollment: 607 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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607 participants in 2 patient groups

Continuous infusion

Experimental group

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 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

Treatment:

Drug: Meropenem

Bolus

Active Comparator group

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): 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

Treatment:

Drug: Meropenem