DeliriumPhase 3Clokin1NCT02466373
Pharmacokinetics and Clinical Effects of Escalating Doses of Clonidine in ICU Patients
A Phase 3 study testing Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml in people with Delirium and Critical Illness, run by Deventer Ziekenhuis at 1 site in Netherlands.
Trial summary
This study is developed for assessing the pharmacodynamic and pharmacokinetic properties of intravenous (IV) clonidine in critically ill patients on the ICU, and to estimate the optimal dosing strategy for IV clonidine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Delirium, Critical Illness
- What is being tested?
- Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteNetherlands
- Study dates
- Dec 2016to 5 Apr 2018
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, a subject must be:
- at least 18 years of age
- intubated
- sedated at the start of the study. Because of the high incidence of delirium on the ICU in all age categories, all age groups > 18 years will be included
Who cannot join
- Severe neurotrauma,
- Severe dementia (living in a nursing home)
- Inability to speak Dutch or English, which is one of the causes of not being able to use the CAM-ICU.
- The use of clonidine during the 96 hours before the start of the study.
- Bradycardia (<50/min)
- Severe hypotension (MAP < 65 after volume resuscitation and vasopressors)
Show all 14Show fewer
- Pregnancy and lactation (pregnancy test are routinely performed in premenopausal women on the ICU).
- Epilepsy
- Known clonidine intolerance
- Liver cirrhosis (Child Pugh class C)
- Recent and acute myocardial infarction
- Severe heart failure (LVEF < 30%)
- Second or third degree atrioventricular (AV)-block without a permanent pacemaker
- Expected transfer to another hospital.
Trial locations and contacts
1 site in 1 country.
About this study
This study is developed for assessing the pharmacodynamic and pharmacokinetic properties of intravenous (IV) clonidine in critically ill patients on the ICU, and to estimate the optimal dosing strategy for IV clonidine.
Read the detailed description
Many patients in intensive care units (ICU's) require sedation and analgesia to tolerate mechanical ventilation and other ICU procedures. Commonly used GABA-ergic anaesthetics like propofol, midazolam and morphine have potential adverse effects that may increase morbidity, prolong ICU stay and provoke delirium. Recent studies have shown that sedation with alpha-2-adrenergic agonists may lead to a reduction of the total amount of gamma-aminobutyric acid (GABA) -ergic anaesthetics and reduction of delirium1In clinical practice the alpha-2-adrenergic agent clonidine is widely used off label as an add-on sedative in mechanically ventilated patients who suffer from delirium, but there are no large studies proving that this therapy is effective and safe. Limited information exists on the pharmacokinetics of iv clonidine, especially in ICU patients. Besides, dosing regimens of clonidine differ widely among ICU's in the Netherlands, and in the literature.
The sample size required for pharmacokinetic modelling with an acceptable level of precision is inversely related to the number of blood samplings taken from each individual. Population pharmacokinetic experiments that have been published have generally used 50 or more subjects. However, in the investigators study a relatively large number of blood samples are taken (>10 per subject when the protocol is completed, see section 6.3). THe investigators estimate that sufficient precision can be obtained with a sample size of 24 subjects, generating an estimated 240 to 360 blood samples.
In a recent publication of a computer simulated population pharmacokinetics of an absorption model using a design that involved 6 samplings per subject, it was estimated that a two-compartment first-order model would need 50 subjects (i.e. 300 blood samplings) to obtain a model with 50% precision and a power of 0.8.
The investigators 24 subjects will be treated with 3 different doses of clonidine (600, 1200 and 1800 µg/day), that is 8 per treatment arm.
On top of this, 8 patients receiving no clonidine will serve as a reference group, in order to interpret hemodynamic and safety data, and to illustrate dose-response relationships.
- Conditions
- Delirium, Critical Illness
- Being tested
- Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml
- Keywords
- clonidine, pharmacodynamics, pharmacokinetics, intensive care, delirium
- Medical subject headings
- Delirium, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 mlDrug
Also called Boehringer Ingelheim, RVG 06055
clonidine intravenous
| Study group | Role | What they receive |
|---|---|---|
| No clonidine | No intervention | No clonidine is administered. The outcome measures are recorded, to compare them with the outcome measures of the other clonidine arms |
| Clonidine 600mcg | Experimental | 4 patients receive 600 µg/day of clonidine without loading schedule. 4 patients receive 600 µg/day of clonidine with a loading schedule of 300 µg in 4 h. Receives: Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml |
| Clonidine 1200mcg | Experimental | * 4 patients receive 1200 µg/day of clonidine without loading schedule.
* 4 patients receive 1200 µg/day of clonidine with a loading schedule of 600 µg in 4 h. Receives: Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml |
| Clonidine 1800mcg | Experimental | * 4 patients receive 1800 µg/day of clonidine without loading schedule.
* 4 patients receive 1800 µg/day of clonidine with a loading schedule of 900 µg in 4 h. Receives: Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml |
What is being measured
The primary outcome is the main question the study is designed to answer.
clonidine plasma concentrations
pharmacokinetic and pharmacodynamic properties of intravenous clonidine in ICU patients Clonidine plasma concentration at start of infusion at t=2, t=4, t=8 and t=12 h Clonidine plasma concentration during study, once daily Clonidine plasma concentration after stopping infusion at t=ω+8, t=ω+16, t=ω+24 h, and t=ω+48 h (ω= end of infusion).
Measured: up to 7 days
Secondary outcomes (4)
heart rate
Heart rate 2-hrly for the first 12 h, 8-hrly thereafter
Measured: up to 7 days
blood pressure
Blood pressure 2-hrly for the first 12 h, 8-hrly thereafter
Measured: up to 7 days
delirium
delirium rating scale, CAM-ICU 3 times daily
Measured: up to 7 days
use of antipsychotics
additional use of haloperidol or sedatives, measured in total amount during the investigational period
Measured: up to 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2015 (estimated)
- Study startDec 2016
- Primary completion5 Apr 2018
- Study completion5 Apr 2018
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 DeliriumStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Deventer Ziekenhuis
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M. Zeeman, Deventer Ziekenhuis
- Investigators
- Huub Oever v/d, Principal investigator, Deventer Ziekenhuis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02466373
- Sponsor's protocol ID
- Clonidine kinetics 1.1
- Acronym
- Clokin1
- Status last verified
- Jul 2018
- First submitted
- 21 Apr 2015
- Last updated
- 30 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
van den Oever HLA, Zeeman M, Klaas E, Nassikovker P, Bles C, de Meijer AR, Kruisdijk-Gerritsen A, Arbouw ME. Safety and tolerability study of clonidine for sedation in mechanically ventilated adult patients. J Anesth Analg Crit Care. 2026 Sep 11;6(1):116. doi: 10.1186/s44158-026-00447-y.
PubMed 42768388
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Clinical Effects of Escalating Doses of Clonidine in ICU Patients
- ClinicalTrials.gov ID
- NCT02466373
- Acronym / sponsor ID
- Clokin1 / Clonidine kinetics 1.1
- Conditions
- Delirium, Critical Illness
- Keywords
- clonidine, pharmacodynamics, pharmacokinetics, intensive care, delirium
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Deventer ZiekenhuisUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- 5 Apr 2018 (actual)
- Study completion
- 5 Apr 2018 (actual)
- First posted
- 9 Jun 2015 (estimated)
- 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.
This study is developed for assessing the pharmacodynamic and pharmacokinetic properties of intravenous (IV) clonidine in critically ill patients on the ICU, and to estimate the optimal dosing strategy for IV clonidine.
Detailed description
Many patients in intensive care units (ICU's) require sedation and analgesia to tolerate mechanical ventilation and other ICU procedures. Commonly used GABA-ergic anaesthetics like propofol, midazolam and morphine have potential adverse effects that may increase morbidity, prolong ICU stay and provoke delirium. Recent studies have shown that sedation with alpha-2-adrenergic agonists may lead to a reduction of the total amount of gamma-aminobutyric acid (GABA) -ergic anaesthetics and reduction of delirium1In clinical practice the alpha-2-adrenergic agent clonidine is widely used off label as an add-on sedative in mechanically ventilated patients who suffer from delirium, but there are no large studies proving that this therapy is effective and safe. Limited information exists on the pharmacokinetics of iv clonidine, especially in ICU patients. Besides, dosing regimens of clonidine differ widely among ICU's in the Netherlands, and in the literature.
The sample size required for pharmacokinetic modelling with an acceptable level of precision is inversely related to the number of blood samplings taken from each individual. Population pharmacokinetic experiments that have been published have generally used 50 or more subjects. However, in the investigators study a relatively large number of blood samples are taken (>10 per subject when the protocol is completed, see section 6.3). THe investigators estimate that sufficient precision can be obtained with a sample size of 24 subjects, generating an estimated 240 to 360 blood samples.
In a recent publication of a computer simulated population pharmacokinetics of an absorption model using a design that involved 6 samplings per subject, it was estimated that a two-compartment first-order model would need 50 subjects (i.e. 300 blood samplings) to obtain a model with 50% precision and a power of 0.8.
The investigators 24 subjects will be treated with 3 different doses of clonidine (600, 1200 and 1800 µg/day), that is 8 per treatment arm.
On top of this, 8 patients receiving no clonidine will serve as a reference group, in order to interpret hemodynamic and safety data, and to illustrate dose-response relationships.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| No clonidine | No intervention | –No clonidine is administered. The outcome measures are recorded, to compare them with the outcome measures of the other clonidine arms |
| Clonidine 600mcg | Experimental | Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml4 patients receive 600 µg/day of clonidine without loading schedule. 4 patients receive 600 µg/day of clonidine with a loading schedule of 300 µg in 4 h. |
| Clonidine 1200mcg | Experimental | Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml* 4 patients receive 1200 µg/day of clonidine without loading schedule. * 4 patients receive 1200 µg/day of clonidine with a loading schedule of 600 µg in 4 h. |
| Clonidine 1800mcg | Experimental | Drug: Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml* 4 patients receive 1800 µg/day of clonidine without loading schedule. * 4 patients receive 1800 µg/day of clonidine with a loading schedule of 900 µg in 4 h. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- at least 18 years of age
- intubated
- sedated at the start of the study. Because of the high incidence of delirium on the ICU in all age categories, all age groups > 18 years will be included
Key exclusion criteria (14 listed)
- Severe neurotrauma,
- Severe dementia (living in a nursing home)
- Inability to speak Dutch or English, which is one of the causes of not being able to use the CAM-ICU.
- The use of clonidine during the 96 hours before the start of the study.
- Bradycardia (<50/min)
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 |
|---|---|---|
| Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 mlAlso: Boehringer Ingelheim, RVG 06055clonidine intravenous | Drug | Clonidine 1200mcg, Clonidine 1800mcg, Clonidine 600mcg |
Primary outcome
clonidine plasma concentrations
Time frame: up to 7 days
pharmacokinetic and pharmacodynamic properties of intravenous clonidine in ICU patients Clonidine plasma concentration at start of infusion at t=2, t=4, t=8 and t=12 h Clonidine plasma concentration during study, once daily Clonidine plasma concentration after stopping infusion at t=ω+8, t=ω+16, t=ω+24 h, and t=ω+48 h (ω= end of infusion).
4 secondary outcomes
heart rate
Time frame: up to 7 days
blood pressure
Time frame: up to 7 days
delirium
Time frame: up to 7 days
use of antipsychotics
Time frame: up to 7 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 30 Jul 2018.
- Derived from this study: PubMed 42768388van den Oever HLA, Zeeman M, Klaas E, Nassikovker P, Bles C, de Meijer AR, Kruisdijk-Gerritsen A, Arbouw ME. Safety and tolerability study of clonidine for sedation in mechanically ventilated adult patients. J Anesth Analg Crit Care. 2026 Sep 11;6(1):116. doi: 10.1186/s44158-026-00447-y.
- 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.
Huub Oever v/d principal investigator
Deventer Ziekenhuis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Clonidine (Catapresan®) 0,150 mg/ml, ampoule 1 ml in people with Delirium and Critical Illness, run by Deventer Ziekenhuis at 1 site in Netherlands.
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 14 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 30 Jul 2018. 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 Netherlands. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
clonidine plasma concentrations (time frame: up to 7 days). 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 NCT02466373, 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 30 Jul 2018.