Bacterial InfectionsPhase 4NCT05586438
Pharmacokinetics of Colistin in Critically-ill Patients With AKI Who Receive SLED
A Phase 4 study testing Colistin Sulfomethate in people with Bacterial Infections, run by Mahidol University at 1 site in Thailand.
Trial summary
Colistin was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time. Dosing recommendations, on the basis of these pharmacokinetic studies, are listed in the drug's product information. Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Bacterial Infections
- What is being tested?
- Colistin Sulfomethate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteThailand
- Study dates
- 18 Oct 2021to 31 Oct 2022
- Phase
- Phase 4
- 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 18 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females greater than 18 years of age.
- All patients will remain in the hospital for pharmacokinetic sampling.
- All subjects must be on the medication colistin as part of their standard of care.
- All subjects must be on sustained low-efficiency dialysis
Who cannot join
- Pregnancy and lactation
- The patients receiving colistin inhalation
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Faculty of Medicine Siriraj Hospital, Mahidol University
Bangkok, 10700
About this study
Official title: Pharmacokinetics of Colistin in Critically-ill Patients With Acute Kidney Injury Who Receive Sustained Low-Efficiency Dialysis
Colistin was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time. Dosing recommendations, on the basis of these pharmacokinetic studies, are listed in the drug's product information. However, there are no optimal dosing recommendations for patients with acute kidney injury who receive sustained low-efficiency dialysis. Furthermore, the science of antibiotic dosing ("pharmacodynamics") has changed significantly since the 1960s and it is quite possible that the dosing recommendations listed in the product information are not optimal. Furthermore, even though physicians refer to "colistin" administration, the only intravenous form of the drug is colistin methanesulfonate (CMS). CMS is converted in the body to colistin. Both CMS and colistin have different pharmacokinetic and antimicrobial activities. For this reason, we, the investigators at the Mahidol university, are performing a pharmacokinetic study of the intravenous CMS/colistin in patients requiring sustained low-efficiency dialysis. Plasma concentrations will be determined around a CMS/colistin dose once the drug has reached steady state. Microbiologic and clinical endpoints will be determined and will be correlated with these concentrations. The measurement of CMS and colistin levels will be determined by a laboratory in Australia.
Read the detailed description
At baseline (upon signing informed consent), the following information will be collected: Demographic data - age, sex, height, weight, state of birth, underlying illnesses, underlying infection, immunosuppression, antibiotic use, laboratory results, current medication use, any other prior medical problems/history and clinical outcomes.
The research coordinator will contact the patient on days 14, 28 and 90 days after the infection to determine clinical outcome. If the patient is still an inpatient the research coordinator will visit the patient in their hospital room to evaluate the patient's health status. This visit will take about 10 minutes. If the patient has been discharged from the hospital, the patient will be contacted by telephone by the research coordinator to determine the health status, if no recent electronic medical record exists. This telephone contact will take about 10 minutes.
Blood work and microbiologic samples to be collected:
Collection of ten samples of 4 mL blood each day during two days of colistin treatment (the dialysis day and non-dialysis day) of colistin therapy will occur. These samples will be collected:
immediately pre-dose, at the end of the colistin infusion, 60 minutes after the end of the colistin infusion, 2 hours after the end of the colistin infusion, 5 hours after the end of the colistin infusion, 8 hours after the end of the colistin infusion, 12 hours after the end of the colistin infusion (or immediately prior to the next dose if the drug is being given every 12 hours).
13 hours after the end of the colistin infusion, 16 hours after the end of the colistin infusion, 20 hours after the end of the colistin infusion, 24 hours after the end of the colistin infusion, Indwelling venous and arterial access lines, if already in place, will be utilized for the pharmacological study's blood draws.
On dialysis day, collection of dialysate fluid will also occur.
60 minutes after the end of the colistin infusion, 3 hours after the end of the colistin infusion, 5 hours after the end of the colistin infusion, 7 hours after the end of the colistin infusion
Rationale: The samples will be utilized for quantification of plasma levels of colistin.
Collection of microbiologic samples within 48-96 hours of the initiation of colistin therapy. These samples are two sets of blood cultures if the patient had bacteremia, a sputum culture if the patient had pneumonia.
Rationale: These samples will be used to determine if there has been rapid bacteriologic clearance of infection.
The blood samples will be processed and stored in a -80° C freezer in a secured laboratory under the supervision of the principal investigator. These samples will then be sent to the laboratory of Drs Jian Li and Roger Nation in Melbourne, Australia, to determine the amount of colistin and CMS that reached the participant's blood following dose administration. All samples will be sent de-identified.
All samples will be analyzed to obtain the amount of colistin and CMS found in the blood. The biologic samples will be under the control of the principal investigator of this research project. To protect confidentiality, all personal identifiers (i.e., name, social security number, and birth date) will be removed (de-identified) and replaced with a specific code number. The information linking these code numbers to the corresponding subjects' identities will be kept in a separate, secure location.
Other items to be collected for study purposes:
An unopened vial of colistin from the same batch as used for the patient will be collected for analysis, so the actual dose of colistin can be calculated.
- Conditions
- Bacterial Infections
- Being tested
- Colistin Sulfomethate
- Keywords
- colistin
- Medical subject headings
- Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colistin SulfomethateDrug
Also called Colistin
The patients receive colistin 150 mg intravenous once daily on non-dialysis day and receive colistin 150 mg intravenous every 12 hours on dialysis day
| Study group | Role | What they receive |
|---|---|---|
| blood draws | Experimental | All patients enrolled will have PK blood samples obtained around a colistin dosing Receives: Drug: Colistin Sulfomethate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration-time curve [AUC]
The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to colistin after administration of a dose of colistin and is expressed in mg*h/L.
Predose, and 1, 2, 5, 8, 12 hours after administration
Measured: 24 hours
Maximum Plasma Concentration [Cmax]
Cmax is the maximum (or peak) serum concentration that colistin achieves in a specified compartment or test area of the body after colistin has been administered and before the administration of a second dose.
Predose, and 1, 2, 5, 8, 12 hours after administration.
Measured: 24 hours
Secondary outcomes (1)
Treatment-Related Adverse Events CTCAE v4.0
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2022
- Study start18 Oct 2021
- Primary completion31 Oct 2022
- Study completion31 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bacterial InfectionsStudies of the same condition, open and under way.
- More trials run by Mahidol UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mahidol University
- Sponsor type
- University, hospital or other
- Collaborators
- Monash University
- Responsible party
- Sponsor
- Investigators
- Adhiratha Boonyasiri, MD, Principal investigator, Mahidol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05586438
- Sponsor's protocol ID
- 223-2564-EC3
- Status last verified
- Nov 2022
- First submitted
- 10 Oct 2022
- Last updated
- 28 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nation RL, Garonzik SM, Thamlikitkul V, Giamarellos-Bourboulis EJ, Forrest A, Paterson DL, Li J, Silveira FP. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis. 2017 Mar 1;64(5):565-571. doi: 10.1093/cid/ciw839. Epub 2016 Dec 23.
PubMed 28011614Jitmuang A, Nation RL, Koomanachai P, Chen G, Lee HJ, Wasuwattakul S, Sritippayawan S, Li J, Thamlikitkul V, Landersdorfer CB. Extracorporeal clearance of colistin methanesulphonate and formed colistin in end-stage renal disease patients receiving intermittent haemodialysis: implications for dosing. J Antimicrob Chemother. 2015;70(6):1804-11. doi: 10.1093/jac/dkv031. Epub 2015 Feb 18.
PubMed 25698772
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Colistin in Critically-ill Patients With Acute Kidney Injury Who Receive Sustained Low-Efficiency Dialysis
- ClinicalTrials.gov ID
- NCT05586438
- Acronym / sponsor ID
- 223-2564-EC3
- Conditions
- Bacterial Infections
- Keywords
- colistin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Mahidol UniversityUniversity, hospital or other
- Collaborators
- Monash University
- Study start
- 18 Oct 2021 (actual)
- Primary completion
- 31 Oct 2022 (actual)
- Study completion
- 31 Oct 2022 (actual)
- First posted
- 19 Oct 2022 (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.
Colistin was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time. Dosing recommendations, on the basis of these pharmacokinetic studies, are listed in the drug's product information. However, there are no optimal dosing recommendations for patients with acute kidney injury who receive sustained low-efficiency dialysis. Furthermore, the science of antibiotic dosing ("pharmacodynamics") has changed significantly since the 1960s and it is quite possible that the dosing recommendations listed in the product information are not optimal. Furthermore, even though physicians refer to "colistin" administration, the only intravenous form of the drug is colistin methanesulfonate (CMS). CMS is converted in the body to colistin. Both CMS and colistin have different pharmacokinetic and antimicrobial activities. For this reason, we, the investigators at the Mahidol university, are performing a pharmacokinetic study of the intravenous CMS/colistin in patients requiring sustained low-efficiency dialysis. Plasma concentrations will be determined around a CMS/colistin dose once the drug has reached steady state. Microbiologic and clinical endpoints will be determined and will be correlated with these concentrations. The measurement of CMS and colistin levels will be determined by a laboratory in Australia.
Detailed description
At baseline (upon signing informed consent), the following information will be collected: Demographic data - age, sex, height, weight, state of birth, underlying illnesses, underlying infection, immunosuppression, antibiotic use, laboratory results, current medication use, any other prior medical problems/history and clinical outcomes.
The research coordinator will contact the patient on days 14, 28 and 90 days after the infection to determine clinical outcome. If the patient is still an inpatient the research coordinator will visit the patient in their hospital room to evaluate the patient's health status. This visit will take about 10 minutes. If the patient has been discharged from the hospital, the patient will be contacted by telephone by the research coordinator to determine the health status, if no recent electronic medical record exists. This telephone contact will take about 10 minutes.
Blood work and microbiologic samples to be collected:
Collection of ten samples of 4 mL blood each day during two days of colistin treatment (the dialysis day and non-dialysis day) of colistin therapy will occur. These samples will be collected:
immediately pre-dose, at the end of the colistin infusion, 60 minutes after the end of the colistin infusion, 2 hours after the end of the colistin infusion, 5 hours after the end of the colistin infusion, 8 hours after the end of the colistin infusion, 12 hours after the end of the colistin infusion (or immediately prior to the next dose if the drug is being given every 12 hours).
13 hours after the end of the colistin infusion, 16 hours after the end of the colistin infusion, 20 hours after the end of the colistin infusion, 24 hours after the end of the colistin infusion, Indwelling venous and arterial access lines, if already in place, will be utilized for the pharmacological study's blood draws.
On dialysis day, collection of dialysate fluid will also occur.
60 minutes after the end of the colistin infusion, 3 hours after the end of the colistin infusion, 5 hours after the end of the colistin infusion, 7 hours after the end of the colistin infusion
Rationale: The samples will be utilized for quantification of plasma levels of colistin.
Collection of microbiologic samples within 48-96 hours of the initiation of colistin therapy. These samples are two sets of blood cultures if the patient had bacteremia, a sputum culture if the patient had pneumonia.
Rationale: These samples will be used to determine if there has been rapid bacteriologic clearance of infection.
The blood samples will be processed and stored in a -80° C freezer in a secured laboratory under the supervision of the principal investigator. These samples will then be sent to the laboratory of Drs Jian Li and Roger Nation in Melbourne, Australia, to determine the amount of colistin and CMS that reached the participant's blood following dose administration. All samples will be sent de-identified.
All samples will be analyzed to obtain the amount of colistin and CMS found in the blood. The biologic samples will be under the control of the principal investigator of this research project. To protect confidentiality, all personal identifiers (i.e., name, social security number, and birth date) will be removed (de-identified) and replaced with a specific code number. The information linking these code numbers to the corresponding subjects' identities will be kept in a separate, secure location.
Other items to be collected for study purposes:
An unopened vial of colistin from the same batch as used for the patient will be collected for analysis, so the actual dose of colistin can be calculated.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| blood draws | Experimental | Drug: Colistin SulfomethateAll patients enrolled will have PK blood samples obtained around a colistin dosing |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males or females greater than 18 years of age.
- All patients will remain in the hospital for pharmacokinetic sampling.
- All subjects must be on the medication colistin as part of their standard of care.
- All subjects must be on sustained low-efficiency dialysis
Key exclusion criteria (2 listed)
- Pregnancy and lactation
- The patients receiving colistin inhalation
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 |
|---|---|---|
| Colistin SulfomethateAlso: ColistinThe patients receive colistin 150 mg intravenous once daily on non-dialysis day and receive colistin 150 mg intravenous every 12 hours on dialysis day | Drug | blood draws |
Primary outcome
Area under the concentration-time curve [AUC]
Time frame: 24 hours
The area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to colistin after administration of a dose of colistin and is expressed in mg*h/L. Predose, and 1, 2, 5, 8, 12 hours after administration
Maximum Plasma Concentration [Cmax]
Time frame: 24 hours
Cmax is the maximum (or peak) serum concentration that colistin achieves in a specified compartment or test area of the body after colistin has been administered and before the administration of a second dose. Predose, and 1, 2, 5, 8, 12 hours after administration.
1 secondary outcome
Treatment-Related Adverse Events CTCAE v4.0
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2022.
- Background: PubMed 28011614Nation RL, Garonzik SM, Thamlikitkul V, Giamarellos-Bourboulis EJ, Forrest A, Paterson DL, Li J, Silveira FP. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis. 2017 Mar 1;64(5):565-571. doi: 10.1093/cid/ciw839. Epub 2016 Dec 23.
- Background: PubMed 25698772Jitmuang A, Nation RL, Koomanachai P, Chen G, Lee HJ, Wasuwattakul S, Sritippayawan S, Li J, Thamlikitkul V, Landersdorfer CB. Extracorporeal clearance of colistin methanesulphonate and formed colistin in end-stage renal disease patients receiving intermittent haemodialysis: implications for dosing. J Antimicrob Chemother. 2015;70(6):1804-11. doi: 10.1093/jac/dkv031. Epub 2015 Feb 18.
- Individual participant dataSharing planned: No
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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.
Adhiratha Boonyasiri, MD principal investigator
Mahidol University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Colistin Sulfomethate in people with Bacterial Infections, run by Mahidol University 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 4 inclusion and 2 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: finished, as of the sponsor's last update on 28 Nov 2022. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the concentration-time curve [AUC] (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05586438, which also lists 2 linked publications.
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 28 Nov 2022.