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

Primary Purpose

Carbapenem-resistant Enterobacteriaceae

Status
Recruiting
Phase
Not Applicable
Locations
Thailand
Study Type
Interventional
Intervention
Collect blood sample
Sponsored by
Phramongkutklao College of Medicine and Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carbapenem-resistant Enterobacteriaceae focused on measuring Tigecycline, Population pharmacokinetics, pharmacokinetics-pharmacodynamics index, bloodstream infection, CRE, Carbapenem-resistant Enterobacteriaceae

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 20 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 Exclusion Criteria: 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

Sites / Locations

  • Phramongkutklao HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention group

Arm Description

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

Outcomes

Primary Outcome Measures

rate constant for tigecycline distribution from the central to the peripheral compartment
Population pharmacokinetic parameter outcome of tigecycline
rate constant for tigecycline distribution from the peripheral to central the compartment
Population pharmacokinetic parameter outcome of tigecycline
elimination rate constant
Population pharmacokinetic parameter of tigecycline
intercompartmental clearance
Population pharmacokinetic parameter outcome of tigecycline
total clearance
Population pharmacokinetic parameter outcome of tigecycline
volume of central compartment
Population pharmacokinetic parameter outcome of tigecycline
volume distribution of peripheral compartment
Population pharmacokinetic parameter outcome of tigecycline
steady state volume distribution
Population pharmacokinetic parameter outcome of tigecycline
Area under the plasma concentration versus time curve (AUC)
Population pharmacokinetic parameter outcome of tigecycline
Peak Plasma Concentration (Cmax)
Population pharmacokinetic parameter outcome of tigecycline

Secondary Outcome Measures

PK/PD index for CRE bloodstream infection
pharmacokinetics-pharmacodynamics parameter of tigecycline for CRE bloodstream infection
Rate of mortality
Alive or death
Number of Participants with the clinical outcome
Clinical cure or clinical failure Clinical cure was defined as the resolution or improvement of all signs and symptoms present at study entry Clinical failure was defined as any one or more following circumstances: persistent or worsened signs and symptoms, a new clinical findings consistent with the progression of infection.
Number of Participants with the microbiological outcome
Eradicated or persistent evaluated by culture of bloodstream
Genotype classification of carbapenemase producing CRE

Full Information

First Posted
July 31, 2023
Last Updated
September 17, 2023
Sponsor
Phramongkutklao College of Medicine and Hospital
Collaborators
Silpakorn University
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1. Study Identification

Unique Protocol Identification Number
NCT06049771
Brief Title
The Population Pharmacokinetics Study of Tigecycline and Pharmacokinetics- Pharmacodynamics Index in Patients With Carbapenem Resistant Enterobacteriaceae Bloodstream Infection
Official Title
The Population Pharmacokinetics Study of Tigecycline and Pharmacokinetics- Pharmacodynamics Index in Patients With Carbapenem Resistant Enterobacteriaceae Bloodstream Infection
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 17, 2023 (Anticipated)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Phramongkutklao College of Medicine and Hospital
Collaborators
Silpakorn University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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 the carbapenem resistance Klebsiella pneumoniae (CR-KP) prevalence increased from 1.1% in 2000 to 17.9% in 2021 and the carbapenem resistance Escherichia coli was increased from 0.6% in 2000 to 5% in 2021. For carbapenemase producing CRE in Thailand was reported blaNDM 47.33%, blaOXA-48 43.33%, and blaNDM+blaOXA-48 6.67%. Ceftazidime-avibactam was first-line of treatment for CRE bloodstream infection recommended by Infectious Disease Society of America 2023 guidance on the treatment of antimicrobial resistant gram-negative infections but ceftazidime-avibactam was limited activity to blaNDM carbapenemase producing CRE. Tigecycline (TGC) was a glycylcyclines antibiotics. TGC was approved for U.S.FDA for complicated intra-abdominal infection, complicated skin and skin structure infection and community acquired pneumonia with loading dose TGC 100 mg then TGC 50 mg q 12 h via intravenous. High dose tigecycline (HD-TGC) loading dose 200 mg then TGC 100 mg q 12 h improve clinical cure in critically ill patients and reduce mortality in CR-KP 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carbapenem-resistant Enterobacteriaceae
Keywords
Tigecycline, Population pharmacokinetics, pharmacokinetics-pharmacodynamics index, bloodstream infection, CRE, Carbapenem-resistant Enterobacteriaceae

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention group
Arm Type
Experimental
Arm Description
Patients who were infected caused by CRE bloodstream infection and were treated with tigecycline. Blood samples were collected.
Intervention Type
Other
Intervention Name(s)
Collect blood sample
Intervention Description
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
Primary Outcome Measure Information:
Title
rate constant for tigecycline distribution from the central to the peripheral compartment
Description
Population pharmacokinetic parameter outcome of tigecycline
Time Frame
up to 6 months
Title
rate constant for tigecycline distribution from the peripheral to central the compartment
Description
Population pharmacokinetic parameter outcome of tigecycline
Time Frame
up to 6 months
Title
elimination rate constant
Description
Population pharmacokinetic parameter of tigecycline
Time Frame
up to 6 months
Title
intercompartmental clearance
Description
Population pharmacokinetic parameter outcome of tigecycline
Time Frame
up to 6 months
Title
total clearance
Description
Population pharmacokinetic parameter outcome of tigecycline
Time Frame
up to 6 months
Title
volume of central compartment
Description
Population pharmacokinetic parameter outcome of tigecycline
Time Frame
up to 6 months
Title
volume distribution of peripheral compartment
Description
Population pharmacokinetic parameter outcome of tigecycline
Time Frame
up to 6 months
Title
steady state volume distribution
Description
Population pharmacokinetic parameter outcome of tigecycline
Time Frame
up to 6 months
Title
Area under the plasma concentration versus time curve (AUC)
Description
Population pharmacokinetic parameter outcome of tigecycline
Time Frame
up to 6 months
Title
Peak Plasma Concentration (Cmax)
Description
Population pharmacokinetic parameter outcome of tigecycline
Time Frame
up to 6 months
Secondary Outcome Measure Information:
Title
PK/PD index for CRE bloodstream infection
Description
pharmacokinetics-pharmacodynamics parameter of tigecycline for CRE bloodstream infection
Time Frame
up to 6 months
Title
Rate of mortality
Description
Alive or death
Time Frame
7,14 and 28 days
Title
Number of Participants with the clinical outcome
Description
Clinical cure or clinical failure Clinical cure was defined as the resolution or improvement of all signs and symptoms present at study entry Clinical failure was defined as any one or more following circumstances: persistent or worsened signs and symptoms, a new clinical findings consistent with the progression of infection.
Time Frame
14 days
Title
Number of Participants with the microbiological outcome
Description
Eradicated or persistent evaluated by culture of bloodstream
Time Frame
7 days
Title
Genotype classification of carbapenemase producing CRE
Time Frame
up to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 20 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sirapat Somsirikarnjanakoon, PharmD.
Phone
0982511524
Email
sirapat.rx@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wichai Santimaleeworagun, PhD.
Phone
0814426713
Email
swichai1234@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sirapat Somsirikarnjanakoon, PharmD.
Organizational Affiliation
Faculty of Pharmacy, Silpakorn University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Wichai Santimaleeworagun, PhD.
Organizational Affiliation
Faculty of Pharmacy, Silpakorn University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Worapong Nasomsong, MD.
Organizational Affiliation
Phramongkutklao College of Medicine and Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Phramongkutklao Hospital
City
Ratchathewi
State/Province
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sirapat Somsirikarnjanakoon, PharmD.
Phone
0982511524
Email
sirapat.rx@gmail.com
First Name & Middle Initial & Last Name & Degree
Wichai Santimaleeworagun, PhD
Phone
0814426713
Email
swichai1234@gmail.com
First Name & Middle Initial & Last Name & Degree
Sirapat Somsirikarnjanakoon, PharmD
First Name & Middle Initial & Last Name & Degree
Wichai Santimaleeworagun, PhD
First Name & Middle Initial & Last Name & Degree
Worapong Nasomsong, MD

12. IPD Sharing Statement

Learn more about this trial

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

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