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

NCT ID: NCT03344627

Last Updated: 2019-03-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

76 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-27

Study Completion Date

2018-12-31

Brief Summary

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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

Detailed Description

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Conditions

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Sepsis Septic Shock Critical Illness Carbapenem Pharmacokinetic Pharmacodynamic Clinical Outcome Organ Failure, Multiple Morality

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Meropenem standard dose

Meropenem 1 g every 8 hours

Group Type ACTIVE_COMPARATOR

Meropenem standard dose

Intervention Type DRUG

* 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.

Meropenem high dose

Meropenem 2 g every 8 hours

Group Type ACTIVE_COMPARATOR

Meropenem high dose

Intervention Type DRUG

* 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

Interventions

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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.

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mahidol University

OTHER

Sponsor Role lead

Responsible Party

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Tospon Lertwattanachai

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tospon Lertwattanachai, B.sc.(Pharm)

Role: PRINCIPAL_INVESTIGATOR

Faculty of Pharmacy, Mahidol University

Locations

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Faculty of Medicine Ramathibodi Hospital

Ratchathewi, Bangkok, Thailand

Site Status

Countries

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Thailand

References

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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.

Reference Type BACKGROUND
PMID: 25753628 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28098629 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27148448 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25038549 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25888181 (View on PubMed)

Mouton JW, van den Anker JN. Meropenem clinical pharmacokinetics. Clin Pharmacokinet. 1995 Apr;28(4):275-86. doi: 10.2165/00003088-199528040-00002.

Reference Type BACKGROUND
PMID: 7648757 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28231816 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32318268 (View on PubMed)

Other Identifiers

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ID07-60-19

Identifier Type: -

Identifier Source: org_study_id

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