Rivastigmine for Intensive Care Unit (ICU) Delirium

Rivastigmine for Delirium in Intensive Care Patients, a Double-blind, Randomized Placebo-controlled add-on Trial

ZonMw: The Netherlands Organisation for Health Research and Development, Novartis, Netherlands Brain Foundation

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.

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.

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

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.

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

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. doi: 10.1016/S0140-6736(10)61855-7. Epub 2010 Nov 4.