Carbapenem, Clinical Outcome, Critical Illness, Morality, Organ Failure, Multiple, Pharmacodynamic, Pharmacokinetic, Sepsis, Septic Shock
Conditions
Brief summary
Sepsis and septic shock patients are considered to have a high risk of complications and death. Appropriate antimicrobial therapy plays an important role in determining outcomes in septic patients. However, pathophysiologic changes associated with critical illness have an impact on pharmacokinetics of antimicrobials. In addition, increasing bacterial resistance is also a growing concern, especially in intensive care units., Consequently, standard antimicrobial dose may not be sufficient to achieve pharmacokinetic/pharmacodynamic target in sepsis and septic shock patients. The purpose of this study is to compare a therapy between meropenem standard dose and meropenem high dose in the treatment of sepsis and septic shock
Interventions
DRUGMeropenem standard dose
* Empirical with 1 g meropenem intravenous infusion in 30 minutes then 1 g intravenous infusion in 3 hours every 8 hours. * Dosage is adjusted in case of renal dysfunction. Duration of therapy is varied regarding source(s) of infection.
DRUGMeropenem high dose
* Empirical with 2 g meropenem intravenous infusion in 30 minutes then 2 g intravenous infusion in 3 hours every 8 hours. * Dosage is adjusted in case of renal dysfunction. Duration of therapy is varied regarding source(s) of infection
Sponsors
Mahidol University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (18 years and older) with sepsis and/or septic shock according to SEPSIS-3 criteria and receive meropenem within 1 hour after diagnosis * Informed consent signed by patient or their legally authorized representative
Exclusion criteria
* Subjects with infective endocarditis * Subjects with central nervous system infection * Subjects who requires surgical condition within 72 hours after randomization * Subjects on extracorporeal membrane oxygenation (ECMO) within 3 days after randomization * Subjects with active seizure * History of receiving meropenem within 1 week prior to randomization * Pregnancy women and lactation * Known allergy to meropenem * Not complete a 72-hour course of empirical meropenem treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SOFA score change | Change from Baseline SOFA score at day 4 | The Sequential organ failure assessment (SOFA) score describe the time course of multiple organ dysfunction. The SOFA score is composed of scores for six organ systems (respiratory, cardiovascular, neurological, hepatic, renal and coagulation). The function of six organ systems is scored from 0 (no organ dysfunction) to 4 (severe organ dysfunction), and the individual organ scores are then summed to a total score between 0 and 24. Primary outcome is assessing change between SOFA score at baseline and SOFA score at day 4 after treatment by meropenem |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical cure | Day 3, 5, 7, 10 and 14 | Composite of: 1. Persistent fever and/or 2. Stable or increased white blood cell count |
| Microbiological cure | Day 3, 5, 7, 10 and 14 | Elimination of the study entry pathogen within 14 days after received meropenem * Bacteremia: no growth in blood cultures * Intra-abdominal infection: no growth in blood cultures * UTI: uropathogen growth of less than 10\^4 CFU/mL in women or less than 10\^3 CFU/mL in men * HAP/VAP: pathogen in sputum culture growth of less than 10\^3 CFU/mL * SSTI: no growth in blood cultures |
| Duration of vasopressor agents | 14 and 28 days | Time interval (day) from time of vasopressor agents initiation to time to vasopressor agents discontinuation |
| Mortality | 14 and 28 days | In hospital mortality |
| Length of ICU stay | 14 and 28 days | Time interval (day) from ICU admission (after randomization) to ICU discharge |
| Length of hospital stay | 14 and 28 days | Time interval (day) from hospital admission (after randomization) to hospital discharge |
| %T > MIC | Day 1 | % time of meropenem concentration above MIC |
| Duration of mechanical ventilator | 14 and 28 days | Time interval (day) of mechanical ventilator |
Countries
Thailand
Outcome results
None listed