Bolus Versus Continuous Infusion of Meropenem
- Conditions
- Antibiotic Resistant InfectionCritical Illness
- Interventions
- Registration Number
- NCT03452839
- Lead Sponsor
- Università Vita-Salute San Raffaele
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 607
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.
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Continuous infusion Meropenem 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 Bolus Meropenem 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
- Primary Outcome Measures
Name Time Method Death or Emergence of new resistant bacteria 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
- Secondary Outcome Measures
Name Time Method Death from any cause day 90 Death from any cause
Cumulative SOFA-free point up to day 28 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.
Antibiotic-free days up to day 28 or death 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 day 28 or death 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
Trial Locations
- Locations (26)
University Hospital Dubrava
🇭🇷Dubrava, Croatia
Astana Medical University
🇰🇿Kazakhstan, Kazakhstan
Federal Clinical & Research Center for Reanimatology and Rehabilitation
🇷🇺Moscow, Russian Federation
I.M. Sechenov Firts Moscow State Medical
🇷🇺Moscow, Russian Federation
Policlinico Univeristario Campus Bio-Medico
🇮🇹Roma, Lazio, Italy
E. O. Ospedali Galliera
🇮🇹Genova, Italy
Università degli Studi della Campania "L. Vanvitelli
🇮🇹Napoli, Italy
AO Città della Salute e della Scienza
🇮🇹Torino, Italy
Università di Udine
🇮🇹Udine, Italy
Ospedale San Lazzaro ASL CN2
🇮🇹Alba, Italy
ASST Cremona
🇮🇹Cremona, Cemona, Italy
Ospedale San Raffaele di Milano
🇮🇹Milan, MI, Italy
A.O.U. Mater Domini
🇮🇹Catanzaro, Reggio Calabria, Italy
Azienda Universitario-Ospedaliera O.O.R.R.
🇮🇹Foggia, Italy
Azienda Ospedaliera Universitaria
🇮🇹Cagliari, Sardegna, Italy
USSL 10 Veneto
🇮🇹San Dona' Di Piave, Venezia, Italy
Grande Ospedale Metropolitano
🇮🇹Reggio Calabria, Italy
Humanitas Research Hospital
🇮🇹Rozzano, Italy
Ospedale A. Cardarelli
🇮🇹Campobasso, Italy
AOU Pisana
🇮🇹Pisa, Italy
Ospedale di Merano
🇮🇹Merano, Italy
Azienda Ospedale - Università Padova - Ospedale "Sant'Antonio
🇮🇹Padova, Italy
A.O.R San Carlo
🇮🇹Potenza, Italy
Città di Lecce Hospital
🇮🇹Lecce, Puglia, Italy
P.O. Pineta Grande - Castelvolturno
🇮🇹Caserta, Italy
Azienda Ospedaliero Universitaria Careggi - Firenze
🇮🇹Firenze, Italy