Carbapenem-resistant EnterobacteriaceaeNCT06049771
The Population Pharmacokinetics Study of Tigecycline and Pharmacokinetics- Pharmacodynamics Index in Patients With Carbapenem Resistant Enterobacteriaceae Bloodstream Infection
A study testing Collect blood sample in people with Carbapenem-resistant Enterobacteriaceae, run by Phramongkutklao College of Medicine and Hospital at 1 site in Thailand.
Trial 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%. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Carbapenem-resistant Enterobacteriaceae
- What is being tested?
- Collect blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteThailand
- Study dates
- 17 Sep 2023to 30 Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Thailand1 site, 1 recruiting
- Recruiting
Phramongkutklao Hospital
Ratchathewi, Bangkok, 10400
Sirapat Somsirikarnjanakoon, PharmD., 0982511524, sirapat.rx@gmail.com
Wichai Santimaleeworagun, PhD, 0814426713, swichai1234@gmail.com
About this study
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.
Read the 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.
- Conditions
- Carbapenem-resistant Enterobacteriaceae
- Being tested
- Collect blood sample
- Keywords
- Tigecycline, Population pharmacokinetics, pharmacokinetics-pharmacodynamics index, bloodstream infection, CRE, Carbapenem-resistant Enterobacteriaceae
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Collect blood sampleOther
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
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Patients who were infected caused by CRE bloodstream infection and were treated with tigecycline. Blood samples were collected. Receives: Other: Collect blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
rate constant for tigecycline distribution from the central to the peripheral compartment
Population pharmacokinetic parameter outcome of tigecycline
Measured: up to 6 months
rate constant for tigecycline distribution from the peripheral to central the compartment
Population pharmacokinetic parameter outcome of tigecycline
Measured: up to 6 months
elimination rate constant
Population pharmacokinetic parameter of tigecycline
Measured: up to 6 months
intercompartmental clearance
Population pharmacokinetic parameter outcome of tigecycline
Measured: up to 6 months
total clearance
Population pharmacokinetic parameter outcome of tigecycline
Measured: up to 6 months
volume of central compartment
Population pharmacokinetic parameter outcome of tigecycline
Measured: up to 6 months
volume distribution of peripheral compartment
Population pharmacokinetic parameter outcome of tigecycline
Measured: up to 6 months
steady state volume distribution
Population pharmacokinetic parameter outcome of tigecycline
Measured: up to 6 months
Area under the plasma concentration versus time curve (AUC)
Population pharmacokinetic parameter outcome of tigecycline
Measured: up to 6 months
Peak Plasma Concentration (Cmax)
Population pharmacokinetic parameter outcome of tigecycline
Measured: up to 6 months
Secondary outcomes (5)
PK/PD index for CRE bloodstream infection
pharmacokinetics-pharmacodynamics parameter of tigecycline for CRE bloodstream infection
Measured: up to 6 months
Rate of mortality
Alive or death
Measured: 7,14 and 28 days
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.
Measured: 14 days
Number of Participants with the microbiological outcome
Eradicated or persistent evaluated by culture of bloodstream
Measured: 7 days
Genotype classification of carbapenemase producing CRE
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2023
- Study start17 Sep 2023 (estimated)
- Primary completion31 May 2025 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carbapenem-resistant EnterobacteriaceaeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Phramongkutklao College of Medicine and Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Silpakorn University
- Responsible party
- Sponsor
- Investigators
- Sirapat Somsirikarnjanakoon, PharmD., Study chair, Faculty of Pharmacy, Silpakorn UniversityWichai Santimaleeworagun, PhD., Study director, Faculty of Pharmacy, Silpakorn UniversityWorapong Nasomsong, MD., Study director, Phramongkutklao College of Medicine and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06049771
- Sponsor's protocol ID
- PMK0009
- Status last verified
- Sep 2023
- First submitted
- 31 Jul 2023
- Last updated
- 22 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Population Pharmacokinetics Study of Tigecycline and Pharmacokinetics- Pharmacodynamics Index in Patients With Carbapenem Resistant Enterobacteriaceae Bloodstream Infection
- ClinicalTrials.gov ID
- NCT06049771
- Acronym / sponsor ID
- PMK0009
- Conditions
- Carbapenem-resistant Enterobacteriaceae
- Keywords
- Tigecycline, Population pharmacokinetics, pharmacokinetics-pharmacodynamics index, bloodstream infection, CRE, Carbapenem-resistant Enterobacteriaceae
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Phramongkutklao College of Medicine and HospitalUniversity, hospital or other
- Collaborators
- Silpakorn University
- Study start
- 17 Sep 2023 (estimated)
- Primary completion
- 31 May 2025 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 22 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Other: Collect blood samplePatients who were infected caused by CRE bloodstream infection and were treated with tigecycline. Blood samples were collected. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Collect blood sampleCollect 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 | Other | Intervention group |
Primary outcome
rate constant for tigecycline distribution from the central to the peripheral compartment
Time frame: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
rate constant for tigecycline distribution from the peripheral to central the compartment
Time frame: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
elimination rate constant
Time frame: up to 6 months
Population pharmacokinetic parameter of tigecycline
intercompartmental clearance
Time frame: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
total clearance
Time frame: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
volume of central compartment
Time frame: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
volume distribution of peripheral compartment
Time frame: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
steady state volume distribution
Time frame: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
Area under the plasma concentration versus time curve (AUC)
Time frame: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
Peak Plasma Concentration (Cmax)
Time frame: up to 6 months
Population pharmacokinetic parameter outcome of tigecycline
5 secondary outcomes
PK/PD index for CRE bloodstream infection
Time frame: up to 6 months
Rate of mortality
Time frame: 7,14 and 28 days
Number of Participants with the clinical outcome
Time frame: 14 days
Number of Participants with the microbiological outcome
Time frame: 7 days
Genotype classification of carbapenemase producing CRE
Time frame: up to 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sirapat Somsirikarnjanakoon, PharmD. study chair
Faculty of Pharmacy, Silpakorn University
Wichai Santimaleeworagun, PhD. study director
Faculty of Pharmacy, Silpakorn University
Worapong Nasomsong, MD. study director
Phramongkutklao College of Medicine and Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Collect blood sample in people with Carbapenem-resistant Enterobacteriaceae, run by Phramongkutklao College of Medicine and Hospital at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sirapat Somsirikarnjanakoon, PharmD. (0982511524, sirapat.rx@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
rate constant for tigecycline distribution from the central to the peripheral compartment (time frame: up to 6 months). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2023.