The Population Pharmacokinetics Study of Tigecycline and Pharmacokinetics- Pharmacodynamics Index in Patients With Carbapenem Resistant Enterobacteriaceae Bloodstream Infection

NCT06049771 | Unknown

• 1 other identifier: PMK0009
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent global public health problem. Patients who were infected caused by CRE bloodstream infection were high mortality up to 40%. The National Antimicrobial Resistance Surveillance Center, Thailand (NARST) reported CRE increased from 1.1% to 17.9%. For carbapenemase producing CRE in Thailand was reported blaNDM 47.33%, blaOXA-48 43.33% and blaNDM+blaOXA-48 6.67%. Tigecycline (TGC) was a glycylcyclines antibiotics. High dose tigecycline (HD-TGC) loading dose 200 mg then TGC 100 mg q 12 h via intravenous improve clinical cure in critically ill patients and reduce mortality in carbapenem resistance Klebsiella pneumoniae bloodstream infection compared with standard dose therapy. TGC has susceptibility to CR-KP 79.6% and has an activity to blaNDM, blaKPC and blaOXA-48 carbapenemase producing CRE. However, TGC has clearance (CL) 0.2-0.3 L/h/kg, and high volume of distribution (vd) 2.8-13 L/kg resulted in low levels of TGC in plasma. Moreover, the pharmacokinetics of TGC in critically ill was limited and inconsistent with the previous study. Now pharmacokinetics-pharmacodynamics index (PK/PD index) of TGC for CRE bloodstream infection was not reported. This study aims to study the population pharmacokinetic and PK-PD index of TGC in patients who were CRE bloodstream infection to increase the success rate of treatment.

Conditions

Carbapenem-resistant Enterobacteriaceae

Keywords

Tigecycline; Population pharmacokinetics; pharmacokinetics-pharmacodynamics index; bloodstream infection; CRE; Carbapenem-resistant Enterobacteriaceae

Outcome Measures

Primary Outcomes (10)

• rate constant for tigecycline distribution from the central to the peripheral compartment

  Population pharmacokinetic parameter outcome of tigecycline

  up to 6 months

• rate constant for tigecycline distribution from the peripheral to central the compartment

  Population pharmacokinetic parameter outcome of tigecycline

  up to 6 months

• elimination rate constant

  Population pharmacokinetic parameter of tigecycline

  up to 6 months

• intercompartmental clearance

  Population pharmacokinetic parameter outcome of tigecycline

  up to 6 months

• total clearance

  Population pharmacokinetic parameter outcome of tigecycline

  up to 6 months

• volume of central compartment

  Population pharmacokinetic parameter outcome of tigecycline

  up to 6 months

• volume distribution of peripheral compartment

  Population pharmacokinetic parameter outcome of tigecycline

  up to 6 months

• steady state volume distribution

  Population pharmacokinetic parameter outcome of tigecycline

  up to 6 months

• Area under the plasma concentration versus time curve (AUC)

  Population pharmacokinetic parameter outcome of tigecycline

  up to 6 months

• Peak Plasma Concentration (Cmax)

  Population pharmacokinetic parameter outcome of tigecycline

  up to 6 months

Secondary Outcomes (5)

• PK/PD index for CRE bloodstream infection

  up to 6 months

• Rate of mortality

  7,14 and 28 days

• Number of Participants with the clinical outcome

  14 days

• Number of Participants with the microbiological outcome

  7 days

• Genotype classification of carbapenemase producing CRE

  up to 6 months

Study Arms (1)

Intervention group

EXPERIMENTAL

Patients who were infected caused by CRE bloodstream infection and were treated with tigecycline. Blood samples were collected.

Other: Collect blood sample

Interventions

Collect blood sample OTHER

Collect blood samples at different time points: after tigecycline administration 1 h, 2-4 h, 4-6 h, 6-11.5 h and 30 minutes before next dose

Intervention group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years and older who were admitted at Phramongkutklao Hospital
• Patients who were diagnosed bloodstream infection with CRE and who were sepsis or septic shock
• Patients who received tigecycline loading dose 200 mg infusion for 1 hour and following maintenance dose 100 mg every 12 h infusion for 1 hour at least 48 hours and grant for blood collection

You may not qualify if:

• Pregnancy or Breastfeeding
• Patients who cannot tolerant to the toxicity of tigecycline for example hypersensitivity to tigecycline or any component of the formulation
• Patients who were infected with more than one isolated in blood culture at the same time

Sponsors & Collaborators

• Phramongkutklao College of Medicine and Hospital: lead
• Silpakorn University: collaborator

Study Sites (1)

Phramongkutklao Hospital

Ratchathewi, Bangkok, 10400, Thailand

RECRUITING

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

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

Study Officials

• Sirapat Somsirikarnjanakoon, PharmD.

  Faculty of Pharmacy, Silpakorn University

  STUDY CHAIR

• Wichai Santimaleeworagun, PhD.

  Faculty of Pharmacy, Silpakorn University

  STUDY DIRECTOR

• Worapong Nasomsong, MD.

  Phramongkutklao College of Medicine and Hospital

  STUDY DIRECTOR

Central Study Contacts

Sirapat Somsirikarnjanakoon, PharmD.

CONTACT

0982511524; sirapat.rx@gmail.com

Wichai Santimaleeworagun, PhD.

CONTACT

0814426713; swichai1234@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: September 22, 2023
• Study Start: September 17, 2023
• Primary Completion: May 31, 2025
• Study Completion: June 30, 2025
• Last Updated: September 22, 2023

Record last verified: 2023-09

Locations

TH (1)