The Effect of Clonidine-enhanced Sedation on Delirium in Ventilated Critically Ill Patients

NCT ID: NCT01876355

Last Updated: 2023-02-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2025-06-30

Brief 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.

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.

Conditions

Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Clonidine

Group Type: EXPERIMENTAL

Clonidine

Intervention Type: DRUG

o 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.

Sodium chloride

Group Type: PLACEBO_COMPARATOR

SodiumChloride

Intervention Type: DRUG

Placebo. Pharmaceutical form: Injection. Route of administration: Intravenous use.

Interventions

Clonidine

o 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.

Intervention Type: DRUG

SodiumChloride

Placebo. Pharmaceutical form: Injection. Route of administration: Intravenous use.

Intervention Type: DRUG

Other Intervention Names

Catapressan; Placebo

Eligibility Criteria

Inclusion Criteria

• Intubated and mechanically ventilated, at the start of the study medication.
• Age > 18 years

Exclusion Criteria

• 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)
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deventer Ziekenhuis

OTHER

Sponsor Role: lead

Responsible Party

Marieke Zeeman

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

H.L.A. van den Oever

Role: PRINCIPAL_INVESTIGATOR

Deventer Ziekenhuis

Locations

Deventer Hospital

Deventer, Overijssel, Netherlands

Countries

Netherlands

Central Contacts

M. Zeeman

Role: CONTACT

M.Zeeman@dz.nl

+31570535045

H.L.A. van den Oever

Role: CONTACT

OevervdH@dz.nl

+31570535353

Facility Contacts

M. Zeeman

Role: primary

M.Zeeman@dz.nl

H.L.A. van den Oever

Role: backup

OevervdH@dz.nl

Other Identifiers

Cat1.1

Identifier Type: -

Identifier Source: org_study_id