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

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ClinicalTrials.gov Identifier: NCT03344627

Recruitment Status : Completed

First Posted : November 17, 2017

Last Update Posted : March 12, 2019

Sponsor:

Information provided by (Responsible Party):

Tospon Lertwattanachai, Mahidol University

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	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
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 :	November 27, 2017
Actual Primary Completion Date :	November 30, 2018
Actual Study Completion Date :	December 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis Shock

Drug Information available for: Meropenem

U.S. FDA Resources

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

Outcome Measures

Primary Outcome Measures :

SOFA score change [ Time Frame: 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 [ Time Frame: 14 and 28 days ]
In hospital mortality
Clinical cure [ Time Frame: Day 3, 5, 7, 10 and 14 ]
Composite of:
1. Persistent fever and/or
2. Stable or increased white blood cell count
Microbiological cure [ Time Frame: 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 [ Time Frame: 14 and 28 days ]
Time interval (day) from time of vasopressor agents initiation to time to vasopressor agents discontinuation
Duration of mechanical ventilator [ Time Frame: 14 and 28 days ]
Time interval (day) of mechanical ventilator
Length of ICU stay [ Time Frame: 14 and 28 days ]
Time interval (day) from ICU admission (after randomization) to ICU discharge
Length of hospital stay [ Time Frame: 14 and 28 days ]
Time interval (day) from hospital admission (after randomization) to hospital discharge
%T > MIC [ Time Frame: Day 1 ]
% time of meropenem concentration above MIC

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03344627

Locations

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Thailand
Faculty of Medicine Ramathibodi Hospital
Ratchathewi, Bangkok, Thailand, 10400

Sponsors and Collaborators

Mahidol University

Investigators

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Principal Investigator:	Tospon Lertwattanachai, B.sc.(Pharm)	Faculty of Pharmacy, Mahidol University

More Information

Publications:

Jaruratanasirikul S, Thengyai S, Wongpoowarak W, Wattanavijitkul T, Tangkitwanitjaroen K, Sukarnjanaset W, Jullangkoon M, Samaeng M. Population pharmacokinetics and Monte Carlo dosing simulations of meropenem during the early phase of severe sepsis and septic shock in critically ill patients in intensive care units. Antimicrob Agents Chemother. 2015;59(6):2995-3001. doi: 10.1128/AAC.04166-14. Epub 2015 Mar 9.

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.

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.

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. Review.

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;19:63. doi: 10.1186/s13054-015-0795-y. Review.

Mouton JW, van den Anker JN. Meropenem clinical pharmacokinetics. Clin Pharmacokinet. 1995 Apr;28(4):275-86. Review.

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. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	Tospon Lertwattanachai, Principal Investigator, Mahidol University
ClinicalTrials.gov Identifier:	NCT03344627
Other Study ID Numbers:	ID07-60-19
First Posted:	November 17, 2017 Key Record Dates
Last Update Posted:	March 12, 2019
Last Verified:	March 2019

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

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Sepsis Toxemia Shock, Septic Shock Critical Illness Multiple Organ Failure Infection	Systemic Inflammatory Response Syndrome Inflammation Pathologic Processes Disease Attributes Meropenem Anti-Bacterial Agents Anti-Infective Agents

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