Clinical Outcome Study of High-dose Meropenem in Sepsis and Septic Shock Patients

Sponsor

Mahidol University (Other)

Overall Status

Completed

CT.gov ID

NCT03344627

Collaborator

(none)

Enrollment

Location

Arms

13.1

Actual Duration (Months)

5.8

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Sepsis Septic Shock Critical Illness Carbapenem Pharmacokinetic Pharmacodynamic Clinical Outcome Organ Failure, Multiple Morality	Drug: Meropenem standard dose Drug: Meropenem high dose	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

76 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Clinical Outcome Study of High-dose Meropenem in Sepsis and Septic Shock Patients

Actual Study Start Date :

Nov 27, 2017

Actual Primary Completion Date :

Nov 30, 2018

Actual Study Completion Date :

Dec 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Meropenem standard dose Meropenem 1 g every 8 hours	Drug: Meropenem 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.
Active Comparator: Meropenem high dose Meropenem 2 g every 8 hours	Drug: Meropenem 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

Arm

Intervention/Treatment

Active Comparator: Meropenem standard dose

Meropenem 1 g every 8 hours

Drug: Meropenem 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.

Active Comparator: Meropenem high dose

Meropenem 2 g every 8 hours

Drug: Meropenem 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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Mortality [14 and 28 days]
In hospital mortality
Clinical cure [Day 3, 5, 7, 10 and 14]
Composite of: Persistent fever and/or 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
Duration of mechanical ventilator [14 and 28 days]
Time interval (day) of mechanical ventilator
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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