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CompletedNCT03344627Updated Mar 12, 2019

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

An interventional study of Meropenem standard dose and Meropenem high dose in Sepsis, Septic Shock and Critical Illness, sponsored by Mahidol University. Completed at 1 site in Thailand. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-03-12.

Sponsored by Mahidol University · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
76
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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

02

Conditions studied

  • Sepsis
  • Septic Shock
  • Critical Illness
  • Carbapenem
  • Pharmacokinetic
  • Pharmacodynamic
  • Clinical Outcome
  • Organ Failure, Multiple
  • Morality
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
76 participants (actual)

Study arms

  • Active comparator
    Meropenem standard dose

    Meropenem 1 g every 8 hours

    Drug: Meropenem standard dose

  • Active comparator
    Meropenem high dose

    Meropenem 2 g every 8 hours

    Drug: Meropenem high dose

Interventions

  • DrugMeropenem 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.

  • DrugMeropenem 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

05

What researchers measure

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

    Time frame: Change from Baseline SOFA score at day 4

Secondary outcomes

  1. Mortality

    In hospital mortality

    Time frame: 14 and 28 days

  2. Clinical cure

    Composite of: 1. Persistent fever and/or 2. Stable or increased white blood cell count

    Time frame: Day 3, 5, 7, 10 and 14

  3. 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

    Time frame: Day 3, 5, 7, 10 and 14

  4. Duration of vasopressor agents

    Time interval (day) from time of vasopressor agents initiation to time to vasopressor agents discontinuation

    Time frame: 14 and 28 days

  5. Duration of mechanical ventilator

    Time interval (day) of mechanical ventilator

    Time frame: 14 and 28 days

  6. Length of ICU stay

    Time interval (day) from ICU admission (after randomization) to ICU discharge

    Time frame: 14 and 28 days

  7. Length of hospital stay

    Time interval (day) from hospital admission (after randomization) to hospital discharge

    Time frame: 14 and 28 days

  8. %T > MIC

    % time of meropenem concentration above MIC

    Time frame: Day 1

06

Study locations

1 site
  • Faculty of Medicine Ramathibodi Hospital
    Ratchathewi, Bangkok 10400, Thailand
07

References and documents

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. PubMed 25753628 ↗
  • 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. PubMed 28098629 ↗
  • 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. PubMed 27148448 ↗
  • 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. PubMed 25038549 ↗
  • 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. PubMed 25888181 ↗
  • Mouton JW, van den Anker JN. Meropenem clinical pharmacokinetics. Clin Pharmacokinet. 1995 Apr;28(4):275-86. doi: 10.2165/00003088-199528040-00002. PubMed 7648757 ↗
  • 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. PubMed 28231816 ↗
  • 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. PubMed 32318268 ↗
08

Registry details

Key details

Study ID
NCT03344627
Lead sponsor
Mahidol University
Responsible party
Tospon Lertwattanachai (Principal Investigator, Mahidol University) — Principal investigator
First posted
Nov 17, 2017
Start date
Nov 27, 2017
Primary completion
Nov 30, 2018
Completion
Dec 31, 2018
Last update
Mar 12, 2019

Study contacts

Tospon Lertwattanachai, B.sc.(Pharm)
principal investigator · Faculty of Pharmacy, Mahidol University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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