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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03344627
• Other study ID #: ID07-60-19
• Status: Completed
• Phase: N/A
• Start date: November 27, 2017
• Est. completion date: December 31, 2018

Study information

• Verified date: March 2019
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 31, 2018
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.
• 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

Locations

Country	Name	City	State
Thailand	Faculty of Medicine Ramathibodi Hospital	Ratchathewi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (7)

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. — View 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. Review. — View Citation

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mortality	In hospital mortality	14 and 28 days
Secondary	Clinical cure	Composite of: Persistent fever and/or; Stable or increased white blood cell count	Day 3, 5, 7, 10 and 14
Secondary	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	Day 3, 5, 7, 10 and 14
Secondary	Duration of vasopressor agents	Time interval (day) from time of vasopressor agents initiation to time to vasopressor agents discontinuation	14 and 28 days
Secondary	Duration of mechanical ventilator	Time interval (day) of mechanical ventilator	14 and 28 days
Secondary	Length of ICU stay	Time interval (day) from ICU admission (after randomization) to ICU discharge	14 and 28 days
Secondary	Length of hospital stay	Time interval (day) from hospital admission (after randomization) to hospital discharge	14 and 28 days
Secondary	%T > MIC	% time of meropenem concentration above MIC	Day 1