Rivastigmine for Intensive Care Unit (ICU) Delirium

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Delirium

Intervention / Treatment
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* Drug: Rivastigmine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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. | Drug: Rivastigmine<br>* 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.<br>* Other names: Exelon;|
| Placebo Comparator: 2<br>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 | Drug: Placebo<br>* Placebo, 2 times a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of delirium |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of delirium |  | 3 months | 
| Use of physical restraints |  | 3 months | 
| Use of escape medication (i.c. Haloperidol or benzodiazepines) |  | 3 months | 
| Number of accidental removed catheters |  | 3 months | 
| Length of ICU stay |  | 3 months | 
| Length of in-hospital stay |  | 3 months | 
| Cognitive outcomes |  | 3 months | 
| Activity of daily living |  | 3 months | 
| Healthcare costs |  | 3 months | 
| Frequency and distribution of side effects |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Delirium, Confusion