Agents Intervening Against Delirium in Intensive Care Unit

Study Overview
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Brief Summary
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Delirium is a frequent condition in the Intensive Care Unit (ICU) with no existing evidence-based treatment. The aim of the AID-ICU study is to assess the benefits and harms of haloperidol treatment for the management of ICU acquired delirium.

Detailed Description
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Delirium among critically ill patients in the intensive care unit (ICU) is a common condition associated with increased morbidity and mortality. No evidence-based treatment exist of this condition. Haloperidol is the most frequently used agent to treat ICU-related delirium, but according to the available literature there is no firm evidence of efficacy and safety of this intervention. AID-ICU aims to assess the benefits and harms of haloperidol in adult, critically ill patients with delirium in the ICU.

Official Title
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Agents Intervening Against Delirium in Intensive Care Unit (AID-ICU) A Randomized, Blinded, Placebo-controlled Trial

Conditions
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Delirium

Intervention / Treatment
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* Drug: Haloperidol Injection
* Other: Saline (0,9%)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute admission to the ICU AND Age ≥ 18 years AND Diagnosed delirium with validated screening Tool as either CAM-ICU or ICDSC Exclusion Criteria: Contraindications to haloperidol Habitual treatment with any antipsychotic medication or treatment with antipsychotics in the ICU prior to inclusion Permanently incompetent (e.g. dementia, mental retardation) Delirium assessment non-applicable (coma or language barriers) Withdrawal from active therapy Fertile women (women < 50) with positive urine human chorionic gonadotropin (hCG) or plasma hCG. Consent according to national regulations not obtainable Patients under coercive measures by regulatory authorities Patients with alcohol-induced delirium (Delirium Tremens)

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
Interventional Model Description: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Haloperidol injection<br>Haloperidol 2,5mg x 3 daily, with additional as needed doses to a maximum of 20mg/daily. Other name: Serenase | Drug: Haloperidol Injection<br>* ICU patients with diagnosed delirium are treated with 2,5mg haloperidol x 3 daily intravenously with additional as needed doses to a maximum of 20mg/daily.<br>* Other names: Serenase;|
| Placebo Comparator: Normal Saline<br>Saline (0,9%) | Other: Saline (0,9%)<br>* ICU patients with diagnosed delirium are treated with 0,5ml isotonic saline x 3 daily and as needed doses to a maximum of 4ml/daily, corresponding to the algorithm in the experimental arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days alive out of the hospital within 90 days post-randomization | Number of days alive and out of hospital | 90 days | 
| 90-day mortality | Death from any cause within 90 days post-randomization | 90 days | 
| Hospital Length of Stay | Total number of days the patient is admitted to any hospital within the 90-day intervention period | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days alive without delirium or coma in the ICU | Number of days where patients are both alive and free of delirium and coma | Until ICU discharge, maximum 90 days | 
| Number of patients with one or more serious adverse reactions to haloperidol and the total number of serious adverse reactions to haloperidol compared with placebo | Serious adverse reactions are: Anaphylactic reactions, Agranulocytosis, Pancytopenia, Ventricular arrhythmia, Extrapyramidal symptoms, Tardive dyskinesia, Malignant Neuroleptic Syndrome, Acute hepatic failure | Measured every day from inclusion until ICU discharge, maximum 90 days | 
| Usage of escape medicine | Number of patients receiving escape medicine and number of days with escape medicine per patients | Measured every day from inclusion until ICU discharge, maximum 90 days | 
| Number of days alive without mechanical ventilation within 90 days postrandomisation | Number of days where patients are both alive and free of mechanical ventilation | Measured every day from inclusion until ICU discharge, maximum 90 days | 
| Mortality | Landmark mortality 1 year post-randomisation | 1 year | 
| Quality of life (five level) | EQ-5D-5L total score 1 year post-randomisation (1-5 of each of the five domains) | 1 year | 
| Quality of life (overall self assessment) | EQ-Visual Analogue Scale 1 year post-randomisation (0-100) | 1 year | 
| Cognitive function 1 year after randomisation at selected sites | Repeated Battery for the Assesment of Neuropsychological Status score 1 year post-randomisation at selected sites (40-150) | 1 year | 
| Executive function 1 year after randomisation at selected sites | Trail Making Test 1 year post-randomisation at selected sites (40-150) | 1 year | 
| A health economic analysis | The analytic details will be based on the primary results of the trial (cost-benefit or cost-minimisation analyses) | 90 days | 
| Cognitive function at admission | Informant Questionnaire on Cognitive Decline in the Elderly at ICU admission at selected sites (40-150) | At inclusion (within the first week) | 

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