Rivastigmine for Intensive Care Unit (ICU) Delirium

This study has been terminated.
(The study is prematurely terminated due to a safety issue)
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Novartis
Hersenstichting
Information provided by:
UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00704301
First received: June 20, 2008
Last updated: August 12, 2010
Last verified: October 2009

June 20, 2008
August 12, 2010
November 2008
April 2010   (final data collection date for primary outcome measure)
Duration of delirium [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Duration of delirium [ Time Frame: end of delirium ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00704301 on ClinicalTrials.gov Archive Site
  • Severity of delirium [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Use of physical restraints [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Use of escape medication (i.c. Haloperidol or benzodiazepines) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Number of accidental removed catheters [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Length of ICU stay [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Length of in-hospital stay [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Cognitive outcomes [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Activity of daily living [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Healthcare costs [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Frequency and distribution of side effects [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • severity of delirium [ Time Frame: during delirium ] [ Designated as safety issue: No ]
  • use of physical restraints [ Time Frame: duration of ICU stay ] [ Designated as safety issue: No ]
  • Use of escape medication (i.c. Haloperidol or benzodiazepines) [ Time Frame: duration of ICU stay ] [ Designated as safety issue: No ]
  • number of accidental removed catheters [ Time Frame: duration of ICU stay ] [ Designated as safety issue: No ]
  • length of ICU stay [ Time Frame: duration of ICU stay ] [ Designated as safety issue: No ]
  • Length of in-hospital stay [ Time Frame: duration of admission ] [ Designated as safety issue: No ]
  • cognitive outcomes [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Activity of daily living [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Healthcare costs [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • frequency and distribution of side effects [ Time Frame: duration of ICU stay ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Rivastigmine for Intensive Care Unit (ICU) Delirium
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Delirium
  • 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.
    Other Name: Exelon
  • Drug: Placebo
    Placebo, 2 times a day
  • 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.
    Intervention: Drug: Rivastigmine
  • 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: 2 times a day
    Intervention: Drug: Placebo
van Eijk MM, Roes KC, Honing ML, Kuiper MA, Karakus A, van der Jagt M, Spronk PE, van Gool WA, van der Mast RC, Kesecioglu J, Slooter AJ. Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicentre, double-blind, placebo-controlled randomised trial. Lancet. 2010 Nov 27;376(9755):1829-37. Epub 2010 Nov 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
104
May 2010
April 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00704301
IC-DEL/009
Yes
Dr. A.J.C. Slooter, university Medical Center Utrecht, the Netherlands
UMC Utrecht
  • ZonMw: The Netherlands Organisation for Health Research and Development
  • Novartis
  • Hersenstichting
Principal Investigator: Arjen JC Slooter, MD. PhD. University Medical Center Utrecht, the Netherlands
UMC Utrecht
October 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP