DeliriumPhase 3CATAPRESNCT01876355
The Effect of Clonidine-enhanced Sedation on Delirium in Ventilated Critically Ill Patients
A Phase 3 study testing Clonidine and SodiumChloride in people with Delirium, run by Deventer Ziekenhuis at 1 site in Netherlands.
Trial summary
Rationale: Delirium is highly prevalent in the ICU. GABA-ergic anaesthetics may provoke delirium. Alpha-2-adrenergic agonists may lead to a reduction of the total amount of GABA-ergic anaesthetics and reduction of delirium. There are no large studies proving that this therapy is effective and safe. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Delirium
- What is being tested?
- Clonidine and SodiumChloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 115 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2024to Jun 2025
- 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
- Intubated and mechanically ventilated, at the start of the study medication.
- Age > 18 years
Who cannot join
- Severe neurotrauma/CVA
- Severe dementia
- Inability to speak Dutch or English
- 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 two vasopressors)
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- Pregnancy
- Epilepsy
- Known clonidine intolerance
- Liver cirrhosis (Child-Pugh Class C)
- Recent and acute myocardial infarction
- Severe heart failure (LVEF<30%)
- Second or third degree AV block
- Renal insufficiency requiring intermittent haemodialysis (CVVH is permitted)
- Expected transfer to another hospital
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Deventer Hospital
Deventer, Overijssel, 7416 SE
M. Zeeman, M.Zeeman@dz.nl
H.L.A. van den Oever, OevervdH@dz.nl
About this study
Official title: The Effect of Clonidine-enhanced Sedation on Delirium in Ventilated Critically Ill Patients CATAPRES (Confusion and Alpha-Two Agonist Prescription Randomised Efficacy Study)
Rationale: Delirium is highly prevalent in the ICU. GABA-ergic anaesthetics may provoke delirium. Alpha-2-adrenergic agonists may lead to a reduction of the total amount of GABA-ergic anaesthetics and reduction of delirium. There are no large studies proving that this therapy is effective and safe.
Objective: The objective of this study is to compare the effect of clonidine with placebo on the occurrence and duration of delirium in mechanically ventilated ICU patients.
Read more
Study design: Prospective randomised double-blind placebo controlled intervention study in 115 patients.
Study population: All patients >18 years old, intubated mechanically ventilated and sedated at inclusion.
Intervention: Clonidine infusion of 0,25 mcg/kg/h added to the standard sedation regimen. Comparison: NaCl 0,9 % infusion as placebo.
Main study parameters/endpoints: The main study parameter is the total number of awake and delirium-free observation periods the first 7 days after randomisation. An observation period is a nursing shift of 8 hours.
Read the detailed description
Rationale: Delirium is highly prevalent in the ICU. It may cause significant morbidity and mortality. One of the factors that may provoke a delirium is the use of GABA-ergic anaesthetics. Recent studies have shown that sedation with alpha-2-adrenergic agonists may lead to a reduction of the total amount of GABA-ergic anaesthetics and reduction of delirium. In clinical practice the alpha-2-adrenergic agent clonidine is used 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.
Objective: The objective of this study is to compare the effect of clonidine with placebo on the occurrence and duration of delirium in mechanically ventilated ICU patients.
Study design: Prospective randomised double-blind placebo controlled intervention study in 115 patients.
Study population: All patients >18 years old, intubated mechanically ventilated and sedated at inclusion.
Intervention: Clonidine infusion of 0,25 mcg/kg/h added to the standard sedation regimen. Comparison: NaCl 0,9 % infusion as placebo.
Main study parameters/endpoints: The main study parameter is the total number of awake and delirium-free observation periods the first 7 days after randomisation. An observation period is a nursing shift of 8 hours.. A delirium-free period is a shift in which the CAM-ICU score is negative.
Secondary endpoints: RASS sedation score, total number of delirium positive observation periods, total amount of sedatives, analgesics and antipsychotics used, organ failure score, ventilation and sedation free days at day 30, mortality.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The burden associated with participation is minimal. All blood samples, CAM-ICU scores and physical examinations required for the study are routine daily practice on the ICU. Adding clonidine for sedation of critically ill patients is common practice in many ICU's in the Netherlands.. Its use is also suggested in the NVIC guideline delirium on the ICU. It is however an off-label treatment. The major side effects of the study medication clonidine are hypertension, hypotension and bradycardia. Smaller studies have shown that these side effects are comparable to midazolam. Hypotension is a phenomenon that occurs very often in ICU patients, and is caused by different conditions, not only by the use of sedative medication. The benefit of participation is the possibility to reduce the period of delirium during ICU stay. Because of the widely off label use of clonidine in sedated and ventilated critically ill ICU patients this study is relevant to test the hypothesis that sedation with clonidine leads to a lower incidence and shorter duration of delirium.
- Conditions
- Delirium
- Being tested
- Clonidine, SodiumChloride
- Keywords
- Delirium, clonidine, ICU, sedation
- Medical subject headings
- Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClonidineDrug
Also called Catapressan
- The concentration of clonidine in the solution is 12.5 µg/ml. Continuous iv infusion of 0.02 ml/kg/h results in a dosage of 0.25 µg/kg/h. The maximum dosage achieved is 25 µg/h. The total amount of clonidine given to a person with a body weight 100 kg or more will be 600 µg a day. Since the doses chosen are in the low range, there will be no dosage adjustment for renal- or liver failure.
SodiumChlorideDrug
Also called Placebo
Placebo. Pharmaceutical form: Injection. Route of administration: Intravenous use.
| Study group | Role | What they receive |
|---|---|---|
| Clonidine | Experimental | Not described Receives: Drug: Clonidine |
| Sodium chloride | Placebo comparator | Not described Receives: Drug: SodiumChloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
CAM-ICU (Confusion Assessment Method for the Intesive Care Unit)
The total amount of delirium-free periods during 7 days after randomisation and start of the study medication. An observation period is a period of 8 hours, coinciding with one nursing shift. A delirium-free period is a shift in which the delirium score is negative.
Measured: 7 days
Secondary outcomes (6)
Signs of agitation
Signs of agitation (for example self removed catheter).
Measured: 7 days
Opiate use
Measured: 7 days
Sedative use
Measured: 7 days
Anti-psychotic use
Measured: 7 days
Ventilation free days
Measured: 7 days
Sedation free days
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2013 (estimated)
- Study startJan 2024 (estimated)
- Primary completionDec 2024 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 115 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Deventer Ziekenhuis
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marieke Zeeman, Deventer Ziekenhuis
- Investigators
- H.L.A. van den Oever, Principal investigator, Deventer Ziekenhuis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01876355
- Sponsor's protocol ID
- Cat1.1
- Acronym
- CATAPRES
- Status last verified
- Feb 2023
- First submitted
- 10 Jun 2013
- Last updated
- 15 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Clonidine-enhanced Sedation on Delirium in Ventilated Critically Ill Patients CATAPRES (Confusion and Alpha-Two Agonist Prescription Randomised Efficacy Study)
- ClinicalTrials.gov ID
- NCT01876355
- Acronym / sponsor ID
- CATAPRES / Cat1.1
- Conditions
- Delirium
- Keywords
- Delirium, clonidine, ICU, sedation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 115 participants (estimated)
- Lead sponsor
- Deventer ZiekenhuisUniversity, hospital or other
- Study start
- Jan 2024 (estimated)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 12 Jun 2013 (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.
Rationale: Delirium is highly prevalent in the ICU. GABA-ergic anaesthetics may provoke delirium. Alpha-2-adrenergic agonists may lead to a reduction of the total amount of GABA-ergic anaesthetics and reduction of delirium. There are no large studies proving that this therapy is effective and safe.
Objective: The objective of this study is to compare the effect of clonidine with placebo on the occurrence and duration of delirium in mechanically ventilated ICU patients.
Study design: Prospective randomised double-blind placebo controlled intervention study in 115 patients.
Study population: All patients >18 years old, intubated mechanically ventilated and sedated at inclusion.
Intervention: Clonidine infusion of 0,25 mcg/kg/h added to the standard sedation regimen. Comparison: NaCl 0,9 % infusion as placebo.
Main study parameters/endpoints: The main study parameter is the total number of awake and delirium-free observation periods the first 7 days after randomisation. An observation period is a nursing shift of 8 hours.
Detailed description
Rationale: Delirium is highly prevalent in the ICU. It may cause significant morbidity and mortality. One of the factors that may provoke a delirium is the use of GABA-ergic anaesthetics. Recent studies have shown that sedation with alpha-2-adrenergic agonists may lead to a reduction of the total amount of GABA-ergic anaesthetics and reduction of delirium. In clinical practice the alpha-2-adrenergic agent clonidine is used 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.
Objective: The objective of this study is to compare the effect of clonidine with placebo on the occurrence and duration of delirium in mechanically ventilated ICU patients.
Study design: Prospective randomised double-blind placebo controlled intervention study in 115 patients.
Study population: All patients >18 years old, intubated mechanically ventilated and sedated at inclusion.
Intervention: Clonidine infusion of 0,25 mcg/kg/h added to the standard sedation regimen. Comparison: NaCl 0,9 % infusion as placebo.
Main study parameters/endpoints: The main study parameter is the total number of awake and delirium-free observation periods the first 7 days after randomisation. An observation period is a nursing shift of 8 hours.. A delirium-free period is a shift in which the CAM-ICU score is negative.
Secondary endpoints: RASS sedation score, total number of delirium positive observation periods, total amount of sedatives, analgesics and antipsychotics used, organ failure score, ventilation and sedation free days at day 30, mortality.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The burden associated with participation is minimal. All blood samples, CAM-ICU scores and physical examinations required for the study are routine daily practice on the ICU. Adding clonidine for sedation of critically ill patients is common practice in many ICU's in the Netherlands.. Its use is also suggested in the NVIC guideline delirium on the ICU. It is however an off-label treatment. The major side effects of the study medication clonidine are hypertension, hypotension and bradycardia. Smaller studies have shown that these side effects are comparable to midazolam. Hypotension is a phenomenon that occurs very often in ICU patients, and is caused by different conditions, not only by the use of sedative medication. The benefit of participation is the possibility to reduce the period of delirium during ICU stay. Because of the widely off label use of clonidine in sedated and ventilated critically ill ICU patients this study is relevant to test the hypothesis that sedation with clonidine leads to a lower incidence and shorter duration of delirium.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clonidine | Experimental | Drug: Clonidine |
| Sodium chloride | Placebo comparator | Drug: SodiumChloride |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Intubated and mechanically ventilated, at the start of the study medication.
- Age > 18 years
Key exclusion criteria (15 listed)
- Severe neurotrauma/CVA
- Severe dementia
- Inability to speak Dutch or English
- 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 |
|---|---|---|
| ClonidineAlso: Catapressano The concentration of clonidine in the solution is 12.5 µg/ml. Continuous iv infusion of 0.02 ml/kg/h results in a dosage of 0.25 µg/kg/h. The maximum dosage achieved is 25 µg/h. The total amount of clonidine given to a person with a body weight 100 kg or more will be 600 µg a day. Since the doses chosen are in the low range, there will be no dosage adjustment for renal- or liver failure. | Drug | Clonidine |
| SodiumChlorideAlso: PlaceboPlacebo. Pharmaceutical form: Injection. Route of administration: Intravenous use. | Drug | Sodium chloride |
Primary outcome
CAM-ICU (Confusion Assessment Method for the Intesive Care Unit)
Time frame: 7 days
The total amount of delirium-free periods during 7 days after randomisation and start of the study medication. An observation period is a period of 8 hours, coinciding with one nursing shift. A delirium-free period is a shift in which the delirium score is negative.
6 secondary outcomes
Signs of agitation
Time frame: 7 days
Opiate use
Time frame: 7 days
Sedative use
Time frame: 7 days
Anti-psychotic use
Time frame: 7 days
Ventilation free days
Time frame: 7 days
Sedation free days
Time frame: 7 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
- 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.
H.L.A. van den Oever 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 and SodiumChloride in people with Delirium, 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 2 inclusion and 15 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 15 Feb 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 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact M. Zeeman (+31570535045, M.Zeeman@dz.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CAM-ICU (Confusion Assessment Method for the Intesive Care Unit) (time frame: 7 days). 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 15 Feb 2023.