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

Primary Purpose

Sepsis, Septic Shock, Critical Illness

Status
Completed
Phase
Not Applicable
Locations
Thailand
Study Type
Interventional
Intervention
Meropenem standard dose
Meropenem high dose
Sponsored by
Mahidol University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Faculty of Medicine Ramathibodi Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Meropenem standard dose

Meropenem high dose

Arm Description

Meropenem 1 g every 8 hours

Meropenem 2 g every 8 hours

Outcomes

Primary Outcome Measures

SOFA score change
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
In hospital mortality
Clinical cure
Composite of: Persistent fever and/or Stable or increased white blood cell count
Microbiological cure
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
Time interval (day) from time of vasopressor agents initiation to time to vasopressor agents discontinuation
Duration of mechanical ventilator
Time interval (day) of mechanical ventilator
Length of ICU stay
Time interval (day) from ICU admission (after randomization) to ICU discharge
Length of hospital stay
Time interval (day) from hospital admission (after randomization) to hospital discharge
%T > MIC
% time of meropenem concentration above MIC

Full Information

First Posted
November 8, 2017
Last Updated
March 9, 2019
Sponsor
Mahidol University
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1. Study Identification

Unique Protocol Identification Number
NCT03344627
Brief Title
Clinical Outcome Study of High-dose Meropenem in Sepsis and Septic Shock Patients
Official Title
Clinical Outcome Study of High-dose Meropenem in Sepsis and Septic Shock Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
November 27, 2017 (Actual)
Primary Completion Date
November 30, 2018 (Actual)
Study Completion Date
December 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mahidol University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Septic Shock, Critical Illness, Carbapenem, Pharmacokinetic, Pharmacodynamic, Clinical Outcome, Organ Failure, Multiple, Morality

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Meropenem standard dose
Arm Type
Active Comparator
Arm Description
Meropenem 1 g every 8 hours
Arm Title
Meropenem high dose
Arm Type
Active Comparator
Arm Description
Meropenem 2 g every 8 hours
Intervention Type
Drug
Intervention Name(s)
Meropenem standard dose
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Meropenem high dose
Intervention Description
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
Primary Outcome Measure Information:
Title
SOFA score change
Description
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
Time Frame
Change from Baseline SOFA score at day 4
Secondary Outcome Measure Information:
Title
Mortality
Description
In hospital mortality
Time Frame
14 and 28 days
Title
Clinical cure
Description
Composite of: Persistent fever and/or Stable or increased white blood cell count
Time Frame
Day 3, 5, 7, 10 and 14
Title
Microbiological cure
Description
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
Time Frame
Day 3, 5, 7, 10 and 14
Title
Duration of vasopressor agents
Description
Time interval (day) from time of vasopressor agents initiation to time to vasopressor agents discontinuation
Time Frame
14 and 28 days
Title
Duration of mechanical ventilator
Description
Time interval (day) of mechanical ventilator
Time Frame
14 and 28 days
Title
Length of ICU stay
Description
Time interval (day) from ICU admission (after randomization) to ICU discharge
Time Frame
14 and 28 days
Title
Length of hospital stay
Description
Time interval (day) from hospital admission (after randomization) to hospital discharge
Time Frame
14 and 28 days
Title
%T > MIC
Description
% time of meropenem concentration above MIC
Time Frame
Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tospon Lertwattanachai, B.sc.(Pharm)
Organizational Affiliation
Faculty of Pharmacy, Mahidol University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Faculty of Medicine Ramathibodi Hospital
City
Ratchathewi
State/Province
Bangkok
ZIP/Postal Code
10400
Country
Thailand

12. IPD Sharing Statement

Citations:
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25753628
Citation
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Citation
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derived

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

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