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

NCT03344627 | Completed DMC

• 1 other identifier: ID07-60-19
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  Change from Baseline SOFA score at day 4

Secondary Outcomes (8)

• Mortality

  14 and 28 days

• Clinical cure

  Day 3, 5, 7, 10 and 14

• Microbiological cure

  Day 3, 5, 7, 10 and 14

• Duration of vasopressor agents

  14 and 28 days

• Duration of mechanical ventilator

  14 and 28 days

Study Arms (2)

Meropenem standard dose

ACTIVE COMPARATOR

Meropenem 1 g every 8 hours

Drug: Meropenem standard dose

Meropenem high dose

ACTIVE COMPARATOR

Meropenem 2 g every 8 hours

Drug: Meropenem high dose

Interventions

Meropenem standard dose 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 standard dose

Meropenem high dose 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

Meropenem high dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

Faculty of Medicine Ramathibodi Hospital

Ratchathewi, Bangkok, 10400, Thailand

Location

Related Publications (8)

• 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.

  PMID: 25753628 BACKGROUND

• 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.

  PMID: 28098629 BACKGROUND

• 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.

  PMID: 27148448 BACKGROUND

• 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.

  PMID: 25038549 BACKGROUND

• 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.

  PMID: 25888181 BACKGROUND

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

  PMID: 7648757 BACKGROUND

• 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.

  PMID: 28231816 BACKGROUND

• 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.

  PMID: 32318268 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic; Critical Illness; Multiple Organ Failure

Interventions

Meropenem

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Disease Attributes

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Tospon Lertwattanachai, B.sc.(Pharm)

  Faculty of Pharmacy, Mahidol University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: November 17, 2017
• Study Start: November 27, 2017
• Primary Completion: November 30, 2018
• Study Completion: December 31, 2018
• Last Updated: March 12, 2019

Record last verified: 2019-03

Locations

TH (1)