ColistinPhase 4COL-ECMO2022NCT05542446
Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation
A Phase 4 study testing Colistin in people with Colistin, run by St. Anne's University Hospital Brno, Czech Republic at 1 site in Czechia.
Trial summary
Colistin is a lipopeptide antibiotic administered as an inactive prodrug - colistin methanesulfonate (CMS). Colistin is a drug with a narrow therapeutic window; the limiting factors are mainly nephrotoxicity and neurotoxicity dependent on plasma concentrations. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Colistin
- What is being tested?
- Colistin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteCzechia
- Study dates
- 1 Sep 2022to 19 Jan 2024
- 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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Men and women (with a negative pregnancy test prior to study enrolment in women of childbearing potential)
- Hospitalized at the Department of Anaesthesiology and Resuscitation, St. Anne´s University Hospital Brno
- Indication for parenteral colistin (or CMS) as part of standard medical care, i.e., in patients with severe bacterial infection
- Informed consent given. In unconscious patients, the study investigator will decide whether to include the patient in the study; this decision is made whenever possible in a medical council consisting of at least one independent physician informed about the study details and one study investigator. An interim informed consent will be given after considering all individual risks. In this case, the Ethics Committee of St. Anne's Hospital in Brno will be informed of the patient's inclusion. The investigator will ask study participants in whom good quality consciousness is restored to give subsequent informed consent without unreasonable delay.
- Additional inclusion criterion:
- For some patients (15 individuals are expected), in addition to all the criteria listed in the Eligibility Criteria section, the following inclusion criterion is provided:
- ECMO support is needed as part of standard therapy for severe respiratory failure.
Who cannot join
- Pregnancy,
- Breast-feeding,
- Refusal to give the informed consent (primarily or after regaining consciousness).
Trial locations and contacts
1 site in 1 country.
About this study
Colistin is a lipopeptide antibiotic administered as an inactive prodrug - colistin methanesulfonate (CMS). Colistin is a drug with a narrow therapeutic window; the limiting factors are mainly nephrotoxicity and neurotoxicity dependent on plasma concentrations. The number of patients with these types of infections, as well as the number of patients requiring extracorporeal membrane oxygenation (ECMO) support for severe respiratory failure, increased significantly in association with COVID-19-induced infections. ECMO can generally affect the pharmacokinetics of drugs by creating a new compartment.
Read the detailed description
The COL-ECMO2022 study is a prospective, non-randomized, open-label single-center, phase IV clinical trial that is designed to assess the influence of ECMO on the pharmacokinetics of colistin and CMS. The study is planned to include up to 30 patients with indication of colistin who will be assigned to one of two arms in a 1:1 ratio depending on the presence/absence of ECMO. All study participants will receive colistin standard, approved dose schedule intravenously. The plasma concentrations of colistin and CMS took at defined intervals will be assessed by high-performance liquid chromatography-mass spectrometry. Patients will participate in the clinical trial for a maximum of three monitored dosing intervals.
Discussion: This study is expected to provide essential evidence-based data on the impact of ECMO on colistin pharmacokinetics in critically ill patients as well as to shed some light on how to optimize the colistin dosing for critically ill patients on ECMO by designing the population model.
- Conditions
- Colistin
- Being tested
- Colistin
- Keywords
- colistin, critically ill, pharmacokinetics, extracorporeal membrane oxygenation, investigator-initiated study
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ColistinDrug
Also called colistin methanesulfonate, colistimethate
Visit 1 - screening - Patient selection phase. Patients meeting the eligibility criteria will be screened if not meeting any of the exclusion criteria. A pregnancy test from a urine test will be performed on women of childbearing potential. The patient will be offered participation in the clinical trial and interviewed by the investigator.
Visit 2 (Visit 8, Visit 14 - optional, only if colistin is still indicated) - CMS administration The patient will be hospitalized at FNUSA. CMS will be given intravenously via the central vein catheter (a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours; only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours).
Visit 3 - Visit 7 (Visit 9-Visit 13, Visit 15-Visit 19 - optional, only if colistin is still indicated) - Pharmacokinetics blood samples collection.
| Study group | Role | What they receive |
|---|---|---|
| Critically ill patients with ECMO | Experimental | The subjects connected to ECMO will be treated with colistin ain approved dosing - a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours. Only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours. Receives: Drug: Colistin |
| Critically ill patients without ECMO | Active comparator | The subjects not connected to ECMO will be treated with colistin ain approved dosing - a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours. Only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours. Receives: Drug: Colistin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Verification of the ECMO-induced changes of colistin or CMS area under the plasma concentration versus time curve (AUC) in critically ill patients.
The primary objective of the clinical trial is to determine the area under the plasma concentration versus time curve of colistin and CMS in critically ill patients with and without ECMO during the dosing interval, calculate and compare the area under the plasma concentration versus time curve of CMS and colistin in each group.
Measured: 24 hours
Secondary outcomes (5)
Model of population pharmacokinetics of colistin in critically ill patients - Cmax
To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The first one is maximum plasma concentrations [Cmax] that will be obtain 2 hours after colistin administration.
Measured: 2 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Model of population pharmacokinetics of colistin in critically ill patients - Tmaxc
To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The second one is time to maximum plasma concentration (Tmaxc) that will be calculated within 2 hours after colistin administration.
Measured: 2 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Model of population pharmacokinetics of colistin in critically ill patients - Tminc
To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The third one is time to minimum plasma concentration (Tminc) that will be calculated within 12 hours after colistin administration.
Measured: 12 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Model of population pharmacokinetics of colistin in critically ill patients - Cmin
To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The fourth one is minimum plasma concentration (Cmin) that will be calculated within 12 hours after colistin administration.
Measured: 12 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Model of population pharmacokinetics of colistin in critically ill patients - AUC
To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The fifth one is Area Under the Curve (AUC) that will be calculated within 24 hours after colistin administration.
Measured: 24 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2022
- Study start1 Sep 2022
- Primary completion19 Jan 2024
- Study completion19 Jan 2024
Why it stopped: After agreement between sponsor and investigator, insufficient patients recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ColistinStudies 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 4
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The primary objective of the clinical trial is to determine the plasma concentrations of colistin and CMS during the one or more monitored dosing interval(s) in critically ill patients with and without ECMO under the real clinical practice conditions; based on these data to calculate and compare the pharmacokinetic parameters (Cmax, Tmax, Ctrough, AUC, Vd, clearance) of CMS and colistin in each group.
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Anne's University Hospital Brno, Czech Republic
- Sponsor type
- University, hospital or other
- Collaborators
- Palacky University
- Responsible party
- Sponsor
- Investigators
- Lucie Tesárková, Scs., Study chair, St. Anne's University Hospital Brno, Czech Republic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05542446
- Sponsor's protocol ID
- COL-ECMO2022
- Other IDs
- 2022-000291-19
- Acronym
- COL-ECMO2022
- Status last verified
- Jan 2024
- First submitted
- 18 Aug 2022
- Last updated
- 31 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Suk P, Rychlickova J, Souckova L, Kubickova V, Urbanek K. Changes of colistin pharmacokinetics in critically ill patients due to the extracorporeal membrane oxygenation: protocol for the COL-ECMO2022 trial - a prospective, non-randomised, open-label phase IV pharmacokinetic clinical trial. BMJ Open. 2023 Jul 30;13(7):e071649. doi: 10.1136/bmjopen-2023-071649.
PubMed 37518089
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation
- ClinicalTrials.gov ID
- NCT05542446
- Acronym / sponsor ID
- COL-ECMO2022 / COL-ECMO2022
- Conditions
- Colistin
- Keywords
- colistin, critically ill, pharmacokinetics, extracorporeal membrane oxygenation, investigator-initiated study
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: After agreement between sponsor and investigator, insufficient patients recruitment
- Enrolment
- 8 participants (actual)
- Lead sponsor
- St. Anne's University Hospital Brno, Czech RepublicUniversity, hospital or other
- Collaborators
- Palacky University
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 19 Jan 2024 (actual)
- Study completion
- 19 Jan 2024 (actual)
- First posted
- 15 Sep 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 is a lipopeptide antibiotic administered as an inactive prodrug - colistin methanesulfonate (CMS). Colistin is a drug with a narrow therapeutic window; the limiting factors are mainly nephrotoxicity and neurotoxicity dependent on plasma concentrations. The number of patients with these types of infections, as well as the number of patients requiring extracorporeal membrane oxygenation (ECMO) support for severe respiratory failure, increased significantly in association with COVID-19-induced infections. ECMO can generally affect the pharmacokinetics of drugs by creating a new compartment.
Detailed description
The COL-ECMO2022 study is a prospective, non-randomized, open-label single-center, phase IV clinical trial that is designed to assess the influence of ECMO on the pharmacokinetics of colistin and CMS. The study is planned to include up to 30 patients with indication of colistin who will be assigned to one of two arms in a 1:1 ratio depending on the presence/absence of ECMO. All study participants will receive colistin standard, approved dose schedule intravenously. The plasma concentrations of colistin and CMS took at defined intervals will be assessed by high-performance liquid chromatography-mass spectrometry. Patients will participate in the clinical trial for a maximum of three monitored dosing intervals.
Discussion: This study is expected to provide essential evidence-based data on the impact of ECMO on colistin pharmacokinetics in critically ill patients as well as to shed some light on how to optimize the colistin dosing for critically ill patients on ECMO by designing the population model.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The primary objective of the clinical trial is to determine the plasma concentrations of colistin and CMS during the one or more monitored dosing interval(s) in critically ill patients with and without ECMO under the real clinical practice conditions; based on these data to calculate and compare the pharmacokinetic parameters (Cmax, Tmax, Ctrough, AUC, Vd, clearance) of CMS and colistin in each group.
| Arm | Type | Receives |
|---|---|---|
| Critically ill patients with ECMO | Experimental | Drug: ColistinThe subjects connected to ECMO will be treated with colistin ain approved dosing - a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours. Only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours. |
| Critically ill patients without ECMO | Active comparator | Drug: ColistinThe subjects not connected to ECMO will be treated with colistin ain approved dosing - a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours. Only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years
- Men and women (with a negative pregnancy test prior to study enrolment in women of childbearing potential)
- Hospitalized at the Department of Anaesthesiology and Resuscitation, St. Anne´s University Hospital Brno
- Indication for parenteral colistin (or CMS) as part of standard medical care, i.e., in patients with severe bacterial infection
- Informed consent given. In unconscious patients, the study investigator will decide whether to include the patient in the study; this decision is made whenever possible in a medical council consisting of at least one independent physician informed about the study details and one study investigator. An interim informed consent will be given after considering all individual risks. In this case, the Ethics Committee of St. Anne's Hospital in Brno will be informed of the patient's inclusion. The investigator will ask study participants in whom good quality consciousness is restored to give subsequent informed consent without unreasonable delay.
Key exclusion criteria (3 listed)
- Pregnancy,
- Breast-feeding,
- Refusal to give the informed consent (primarily or after regaining consciousness).
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 |
|---|---|---|
| ColistinAlso: colistin methanesulfonate, colistimethateVisit 1 - screening - Patient selection phase. Patients meeting the eligibility criteria will be screened if not meeting any of the exclusion criteria. A pregnancy test from a urine test will be performed on women of childbearing potential. The patient will be offered participation in the clinical trial and interviewed by the investigator. Visit 2 (Visit 8, Visit 14 - optional, only if colistin is still indicated) - CMS administration The patient will be hospitalized at FNUSA. CMS will be given intravenously via the central vein catheter (a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours; only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours). Visit 3 - Visit 7 (Visit 9-Visit 13, Visit 15-Visit 19 - optional, only if colistin is still indicated) - Pharmacokinetics blood samples collection. | Drug | Critically ill patients with ECMO, Critically ill patients without ECMO |
Primary outcome
Verification of the ECMO-induced changes of colistin or CMS area under the plasma concentration versus time curve (AUC) in critically ill patients.
Time frame: 24 hours
The primary objective of the clinical trial is to determine the area under the plasma concentration versus time curve of colistin and CMS in critically ill patients with and without ECMO during the dosing interval, calculate and compare the area under the plasma concentration versus time curve of CMS and colistin in each group.
5 secondary outcomes
Model of population pharmacokinetics of colistin in critically ill patients - Cmax
Time frame: 2 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Model of population pharmacokinetics of colistin in critically ill patients - Tmaxc
Time frame: 2 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Model of population pharmacokinetics of colistin in critically ill patients - Tminc
Time frame: 12 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Model of population pharmacokinetics of colistin in critically ill patients - Cmin
Time frame: 12 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Model of population pharmacokinetics of colistin in critically ill patients - AUC
Time frame: 24 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Results and safety
The study was stopped early (reason given: After agreement between sponsor and investigator, insufficient patients recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
- Derived from this study: PubMed 37518089Suk P, Rychlickova J, Souckova L, Kubickova V, Urbanek K. Changes of colistin pharmacokinetics in critically ill patients due to the extracorporeal membrane oxygenation: protocol for the COL-ECMO2022 trial - a prospective, non-randomised, open-label phase IV pharmacokinetic clinical trial. BMJ Open. 2023 Jul 30;13(7):e071649. doi: 10.1136/bmjopen-2023-071649.
- Individual participant dataSharing planned: No
Related trials for Colistin
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Hospital Acquired Bacterial Pneumonia (HABP), Ventilator Associated Bacterial Pneumonia (VABP)
Not yet recruitingPhase 2/3
Nebulised Colistimethate Sodium to Prevent Pediatric Ventilator-associated Pneumonia
Ventilator Associated Pneumonia
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Inhaled Colistin to Prevent Ventilator-Associated Pneumonia in Patients With Acute Brain Injury
Ventilator-Associated Pneumonia (VAP), Inha'le'd
Active, not recruitingPhase 4
Colistin and Meropenem Versus Amikacin and Meropenem for MDR Gram Negative Bacteria Regarding Efficacy and Safety.
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Not yet recruitingPhase 3
Colistin Nephrotoxicity and Role of Alpha Lipoic Acid
Nephrotoxicity
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.
Lucie Tesárková, Scs. study chair
St. Anne's University Hospital Brno, Czech Republic
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 in people with Colistin, run by St. Anne's University Hospital Brno, Czech Republic at 1 site in Czechia.
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 8 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: stopped early, as of the sponsor's last update on 31 Jan 2024. 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 Czechia. 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 was stopped early (reason given: After agreement between sponsor and investigator, insufficient patients recruitment). Results are not available in the source record.
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?
Verification of the ECMO-induced changes of colistin or CMS area under the plasma concentration versus time curve (AUC) in critically ill patients. (time frame: 24 hours). 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 NCT05542446, which also lists 1 linked publication.
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 31 Jan 2024.