Official Title: “Rivastigmine for Delirium in Intensive Care Patients, a Double-Blind, Randomized Placebo-Controlled Add-on Trial”

Delirium in Intensive Care (IC) patients is a frequent disorder. The aim of this study is to investigate whether treatment of delirium in the ICU with rivastigmine added to haloperidol shortens the duration of delirium in comparison to placebo added to the treatment with haloperidol.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: November 2010

Objective: To study whether rivastigmine added to treatment with haloperidol shortens the duration of delirium in ICU patients and reduces costs.

Study design: Multicentre, double-blind, randomized controlled trial. Study population:

Consecutive adult ICU patients with delirium according to the CAM-ICU.

Intervention: Increasing dosage of rivastigmine or placebo as add-on medication.

Primary study parameters: Duration of delirium. Secondary study parameters: Delirium severity, length of ICU and hospital stay, functional status and mortality after 3 months.

Sample size: 440 patients will be included. Economic evaluation: includes a comparison of direct and indirect medical costs.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Burden: questionnaires (duration: 30 minutes).

Risk: possible exposure to drug not indicated for the disorder. Benefit: possible treatment with according to experts possible beneficial drug.

Consideration: The investigators of this study believe that the burden and risk do not exceed the expected benefit.

Intervention(s) in this Clinical Trial

• Drug: Rivastigmine
  • Rivastigmine, two times 1,5 mg a day. The dosage will be increased every three days with 3 mg a day, until the CAM-ICU is negative or until the occurrence of presumed severe adverse effects or until a maximum of 12 mg a day.
• Drug: Placebo
  • Placebo, 3 times a day

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Haloperidol: aged 70 years or less: 1 mg haloperidol three times a day i.v. older than 70 years: 0,5 mg haloperidol three times a day i.v. Rivastigmine: two times 1,5 mg a day; The dosage will be increased every three days with 3 mg a day, until the CAM-ICU is negative or until the occurrence of presumed severe adverse effects or until a maximum of 12 mg a day.
• Placebo Comparator: 2
  • Haloperidol: aged 70 years or less: 1 mg haloperidol three times a day i.v. older than 70 years: 0,5 mg haloperidol three times a day i.v. Placebo: 3 times a day

Primary Measures

• Duration of delirium
  • Time Frame: 3 months
    Safety Issue?: No

Secondary Measures

• Severity of delirium
  • Time Frame: 3 months
    Safety Issue?: No
• Use of physical restraints
  • Time Frame: 3 months
    Safety Issue?: No
• Use of escape medication (i.c. Haloperidol or benzodiazepines)
  • Time Frame: 3 months
    Safety Issue?: No
• Number of accidental removed catheters
  • Time Frame: 3 months
    Safety Issue?: No
• Length of ICU stay
  • Time Frame: 3 months
    Safety Issue?: No
• Length of in-hospital stay
  • Time Frame: 3 months
    Safety Issue?: No
• Cognitive outcomes
  • Time Frame: 3 months
    Safety Issue?: No
• Activity of daily living
  • Time Frame: 3 months
    Safety Issue?: No
• Healthcare costs
  • Time Frame: 3 months
    Safety Issue?: No
• Frequency and distribution of side effects
  • Time Frame: 3 months
    Safety Issue?: Yes

Inclusion Criteria:

• 18 years or older
• Positive CAM-ICU

Exclusion Criteria:

• Known allergy to rivastigmine
• Unable to receive enteric medication
• Pregnant or lactating
• Renal replacement therapy
• Hepatic encephalopathy
• Second or third degree atrioventricular block
• Uncertainty about diagnosis delirium and no confirmation by neurologist, psychiatrist or geriatrician
• Parkinson's disease.
• Lewy body dementia.
• ECG QT interval above 500 msec.
• No informed consent

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: UMC Utrecht

Overall Clinical Trial Officials and Contacts

Arjen JC Slooter, MD. PhD. Principal Investigator University Medical Center Utrecht, the Netherlands  

Overall Contact: Arjen JC Slooter, MD., PhD. 31-88-755-3261 a.slooter-3@umcutrecht.nl

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00704301

Study ID Number: IC-DEL/008

ClinicalTrials.gov Identifier: NCT00704301

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)