Agents Intervening Against Delirium in Intensive Care Unit (AID-ICU)

• ClinicalTrials.gov Identifier: NCT03392376
• Recruitment Status: Active, not recruiting
• First Posted: January 8, 2018
• Last Update Posted: January 18, 2023
• Sponsor: Zealand University Hospital
• Collaborators: Centre for Research in Intensive Care (CRIC); Copenhagen Trial Unit, Center for Clinical Intervention Research; Scandinavian Critical Care Trials Group; The Danish Centre of Applied Social Science (VIVE)
• Information provided by (Responsible Party): Zealand University Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Delirium	Drug: Haloperidol Injection; Other: Saline (0,9%)	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Agents Intervening Against Delirium in Intensive Care Unit (AID-ICU) A Randomized, Blinded, Placebo-controlled Trial
• Actual Study Start Date: June 13, 2018
• Actual Primary Completion Date: July 9, 2022
• Estimated Study Completion Date: July 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Haloperidol injection; Haloperidol 2,5mg x 3 daily, with additional as needed doses to a maximum of 20mg/daily. Other name: Serenase	Drug: Haloperidol Injection; 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.; Other Name: Serenase
Placebo Comparator: Normal Saline; Saline (0,9%)	Other: Saline (0,9%); 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.

Outcome Measures

Primary Outcome Measures :

1. Days alive out of the hospital within 90 days post-randomization [ Time Frame: 90 days ]
   Number of days alive and out of hospital
2. 90-day mortality [ Time Frame: 90 days ]
   Death from any cause within 90 days post-randomization
3. Hospital Length of Stay [ Time Frame: 90 days ]
   Total number of days the patient is admitted to any hospital within the 90-day intervention period

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

Denmark

Dept. Intensive Care, Aabenraa Hospital

Aabenraa, Denmark, 6200

Dept. of Intensive Care, Aalborg University Hospital

Aalborg, Denmark, 9000

Dept. of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet

Copenhagen, Denmark, 2100

Dept. of Intensive Care, Herlev Hospital

Herlev, Denmark, 2730

Dept. of Intensive Care, Herning Hospital

Herning, Denmark, 7400

Dept. of Intensive Care, Nordsjaelland Hospital

Hillerød, Denmark, 3400

Regionshospitalet Nordjylland, Hjørring

Hjørring, Denmark, 9800

Dept. of Intensive Care, Holstebro Hospital

Holstebro, Denmark, 7500

Dept. of Intensive Care, Zealand University Hospital, Køge

Køge, Denmark, 4600

Dept. of Intensive Care, Nykøbing Falster Hospital

Nykøbing Falster, Denmark, 4800

Dept of intensive care, Odense University Hospital

Odense, Denmark, 5000

Dept. of Intensive Care, Zealand University Hospital Roskilde

Roskilde, Denmark, 4000

Dept. of Intensive Care, Sønderborg Hospital

Sønderborg, Denmark, 6400

Finland

Dept. of Intensive Care, Helsinki University Central Hospital

Helsinki, Finland, 00120

Italy

Dept. of Neurosurgical Intensive Care, San Gerardo Hospital, Monza.

Monza, Italy

United Kingdom

UHW Adult Critical Care Cardiff

Cardiff, United Kingdom, CF14 4XW

Sponsors and Collaborators

Zealand University Hospital

Centre for Research in Intensive Care (CRIC)

Copenhagen Trial Unit, Center for Clinical Intervention Research

Scandinavian Critical Care Trials Group

The Danish Centre of Applied Social Science (VIVE)

Investigators

• Study Chair: OIe Mathiesen, MD, PhD; Zealand University Hospital
• Study Chair: Anders Perner, MD,PhD; Rigshospitalet, Denmark
• Study Chair: Jørn Wetterslev, MD, PhD; Copenhagen Trial Unit, Center for Clinical Intervention Research

More Information

Additional Information:

LINK to the AID-ICU webpage 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Andersen-Ranberg NC, Poulsen LM, Perner A, Wetterslev J, Estrup S, Hastbacka J, Morgan M, Citerio G, Caballero J, Lange T, Kjaer MN, Ebdrup BH, Engstrom J, Olsen MH, Oxenboll Collet M, Mortensen CB, Weber SO, Andreasen AS, Bestle MH, Uslu B, Scharling Pedersen H, Gramstrup Nielsen L, Toft Boesen HC, Jensen JV, Nebrich L, La Cour K, Laigaard J, Haurum C, Olesen MW, Overgaard-Steensen C, Westergaard B, Brand B, Kingo Vesterlund G, Thornberg Kyhnauv P, Mikkelsen VS, Hyttel-Sorensen S, de Haas I, Aagaard SR, Nielsen LO, Eriksen AS, Rasmussen BS, Brix H, Hildebrandt T, Schonemann-Lund M, Fjeldsoe-Nielsen H, Kuivalainen AM, Mathiesen O; AID-ICU Trial Group. Haloperidol for the Treatment of Delirium in ICU Patients. N Engl J Med. 2022 Dec 29;387(26):2425-2435. doi: 10.1056/NEJMoa2211868. Epub 2022 Oct 26.

• Responsible Party: Zealand University Hospital
• ClinicalTrials.gov Identifier: NCT03392376
• Other Study ID Numbers: REG-169-2017
• First Posted: January 8, 2018
• Last Update Posted: January 18, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Zealand University Hospital:

ICU Delirium; Haloperidol

Additional relevant MeSH terms:

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Haloperidol; Haloperidol decanoate; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Dopamine Antagonists; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Dyskinesia Agents