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
About this trial
This is an interventional treatment trial for Sepsis
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
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
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:
PubMed Identifier
25753628
Citation
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Results Reference
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PubMed Identifier
28098629
Citation
Roberts JA, Kumar A, Lipman J. Right Dose, Right Now: Customized Drug Dosing in the Critically Ill. Crit Care Med. 2017 Feb;45(2):331-336. doi: 10.1097/CCM.0000000000002210.
Results Reference
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PubMed Identifier
27148448
Citation
Suwantarat N, Carroll KC. Epidemiology and molecular characterization of multidrug-resistant Gram-negative bacteria in Southeast Asia. Antimicrob Resist Infect Control. 2016 May 4;5:15. doi: 10.1186/s13756-016-0115-6. eCollection 2016.
Results Reference
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PubMed Identifier
25038549
Citation
Blot SI, Pea F, Lipman J. The effect of pathophysiology on pharmacokinetics in the critically ill patient--concepts appraised by the example of antimicrobial agents. Adv Drug Deliv Rev. 2014 Nov 20;77:3-11. doi: 10.1016/j.addr.2014.07.006. Epub 2014 Jul 15.
Results Reference
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PubMed Identifier
25888181
Citation
Marquet K, Liesenborgs A, Bergs J, Vleugels A, Claes N. Incidence and outcome of inappropriate in-hospital empiric antibiotics for severe infection: a systematic review and meta-analysis. Crit Care. 2015 Feb 16;19(1):63. doi: 10.1186/s13054-015-0795-y.
Results Reference
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PubMed Identifier
7648757
Citation
Mouton JW, van den Anker JN. Meropenem clinical pharmacokinetics. Clin Pharmacokinet. 1995 Apr;28(4):275-86. doi: 10.2165/00003088-199528040-00002.
Results Reference
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PubMed Identifier
28231816
Citation
de Grooth HJ, Geenen IL, Girbes AR, Vincent JL, Parienti JJ, Oudemans-van Straaten HM. SOFA and mortality endpoints in randomized controlled trials: a systematic review and meta-regression analysis. Crit Care. 2017 Feb 24;21(1):38. doi: 10.1186/s13054-017-1609-1.
Results Reference
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Citation
Lertwattanachai T, Montakantikul P, Tangsujaritvijit V, Sanguanwit P, Sueajai J, Auparakkitanon S, Dilokpattanamongkol P. Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial. J Intensive Care. 2020 Apr 15;8:26. doi: 10.1186/s40560-020-00442-7. eCollection 2020.
Results Reference
derived
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Clinical Outcome Study of High-dose Meropenem in Sepsis and Septic Shock Patients
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