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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2013 by Deventer Ziekenhuis
Sponsor:
Information provided by (Responsible Party):
M. Zeeman, Deventer Ziekenhuis
ClinicalTrials.gov Identifier:
NCT01876355
First received: June 10, 2013
Last updated: June 13, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Delirium
Drug: Clonidine
Drug: SodiumChloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Deventer Ziekenhuis:

Primary Outcome Measures:
  • CAM-ICU (Confusion Assessment Method for the Intesive Care Unit) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Signs of agitation [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Signs of agitation (for example self removed catheter).

  • Opiate use [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Sedative use [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Anti-psychotic use [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Ventilation free days [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Sedation free days [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 115
Study Start Date: September 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clonidine Drug: 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.
Other Name: Catapressan
Placebo Comparator: Sodium chloride Drug: SodiumChloride
Placebo. Pharmaceutical form: Injection. Route of administration: Intravenous use.
Other Name: Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01876355

Contacts
Contact: M. Zeeman M.Zeeman@dz.nl
Contact: H.L.A. van den Oever OevervdH@dz.nl

Locations
Netherlands
Deventer Ziekenhuis
Deventer, Overijssel, Netherlands, 7416 SE
Sponsors and Collaborators
Deventer Ziekenhuis
  More Information

No publications provided

Responsible Party: M. Zeeman, Principal Investigator, Deventer Ziekenhuis
ClinicalTrials.gov Identifier: NCT01876355     History of Changes
Other Study ID Numbers: Cat1.1
Study First Received: June 10, 2013
Last Updated: June 13, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Deventer Ziekenhuis:
Delirium, Sedation, clonidine, midazolam, mechanical ventilation, delirium, agitation

Additional relevant MeSH terms:
Delirium
Delirium, Dementia, Amnestic, Cognitive Disorders
Critical Illness
Disease Attributes
Pathologic Processes
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Mental Disorders
Clonidine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antihypertensive Agents
Cardiovascular Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014