DeliriumPhase 4AID-ICUNCT03392376
Agents Intervening Against Delirium in Intensive Care Unit
A Phase 4 study testing Haloperidol Injection and Saline (0,9%) in people with Delirium, run by Zealand University Hospital at 16 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Delirium
- What is being tested?
- Haloperidol Injection and Saline (0,9%)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,000 participants
- Where
- 16 sitesin 4 countries
- Study dates
- 13 Jun 2018to Jul 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute admission to the ICU AND
- Age ≥ 18 years AND
- Diagnosed delirium with validated screening Tool as either CAM-ICU or ICDSC
Who cannot join
- 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.
Show all 9Show fewer
- Consent according to national regulations not obtainable
- Patients under coercive measures by regulatory authorities
- Patients with alcohol-induced delirium (Delirium Tremens)
Trial locations and contacts
16 sites in 4 countries.
16 sites in 4 countries
Denmark13 sites
Dept. Intensive Care, Aabenraa Hospital
Aabenraa, 6200
Dept. of Intensive Care, Aalborg University Hospital
Aalborg, 9000
Dept. of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet
Copenhagen, 2100
Dept. of Intensive Care, Herlev Hospital
Herlev, 2730
Dept. of Intensive Care, Herning Hospital
Herning, 7400
Dept. of Intensive Care, Nordsjaelland Hospital
Hillerød, 3400
Regionshospitalet Nordjylland, Hjørring
Hjørring, 9800
Dept. of Intensive Care, Holstebro Hospital
Holstebro, 7500
Dept. of Intensive Care, Zealand University Hospital, Køge
Køge, 4600
Dept. of Intensive Care, Nykøbing Falster Hospital
Nykøbing Falster, 4800
Dept of intensive care, Odense University Hospital
Odense, 5000
Dept. of Intensive Care, Zealand University Hospital Roskilde
Roskilde, 4000
Dept. of Intensive Care, Sønderborg Hospital
Sønderborg, 6400
Finland1 site
Dept. of Intensive Care, Helsinki University Central Hospital
Helsinki, 00120
Italy1 site
Dept. of Neurosurgical Intensive Care, San Gerardo Hospital, Monza.
Monza
About this study
Official title: Agents Intervening Against Delirium in Intensive Care Unit (AID-ICU) A Randomized, Blinded, Placebo-controlled Trial
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.
Read the 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.
- Conditions
- Delirium
- Being tested
- Haloperidol Injection, Saline (0,9%)
- Keywords
- ICU Delirium, Haloperidol
- Medical subject headings
- Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haloperidol InjectionDrug
Also called Serenase
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.
Saline (0,9%)Other
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.
| Study group | Role | What they receive |
|---|---|---|
| Haloperidol injection | Experimental | Haloperidol 2,5mg x 3 daily, with additional as needed doses to a maximum of 20mg/daily.
Other name: Serenase Receives: Drug: Haloperidol Injection |
| Normal Saline | Placebo comparator | Saline (0,9%) Receives: Other: Saline (0,9%) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days alive out of the hospital within 90 days post-randomization
Number of days alive and out of hospital
Measured: 90 days
90-day mortality
Death from any cause within 90 days post-randomization
Measured: 90 days
Hospital Length of Stay
Total number of days the patient is admitted to any hospital within the 90-day intervention period
Measured: 90 days
Secondary outcomes (11)
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
Measured: 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: 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: 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: Measured every day from inclusion until ICU discharge, maximum 90 days
Mortality
Landmark mortality 1 year post-randomisation
Measured: 1 year
Quality of life (five level)
EQ-5D-5L total score 1 year post-randomisation (1-5 of each of the five domains)
Measured: 1 year
Quality of life (overall self assessment)
EQ-Visual Analogue Scale 1 year post-randomisation (0-100)
Measured: 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)
Measured: 1 year
Executive function 1 year after randomisation at selected sites
Trail Making Test 1 year post-randomisation at selected sites (40-150)
Measured: 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)
Measured: 90 days
Cognitive function at admission
Informant Questionnaire on Cognitive Decline in the Elderly at ICU admission at selected sites (40-150)
Measured: At inclusion (within the first week)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2018
- Study start13 Jun 2018
- Primary completion9 Jul 2022
- Study completionJul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- More trials run by Zealand University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- 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)
- Responsible party
- Sponsor
- Investigators
- OIe Mathiesen, MD, PhD, Study chair, Zealand University HospitalAnders Perner, MD,PhD, Study chair, Copenhagen University Hospital, RigshospitaletJørn Wetterslev, MD, PhD, Study chair, Copenhagen Trial Unit, Center for Clinical Intervention Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03392376
- Sponsor's protocol ID
- REG-169-2017
- Acronym
- AID-ICU
- Status last verified
- Jan 2023
- First submitted
- 30 Nov 2017
- Last updated
- 18 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Andersen-Ranberg NC, Poulsen LM, Perner A, Hastbacka J, Morgan M, Citerio G, Damby SE, Mortensen CB, Collet MO, Weber SO, Andreasen AS, Bestle M, Uslu B, Pedersen HS, Nielsen LG, Damgaard K, Jensen TB, Sommer T, Dey N, Mathiesen O, Granholm A. Haloperidol for Hypoactive and Hyperactive Delirium in ICU Patients-A Post Hoc Bayesian Analysis of the AID-ICU Trial. Acta Anaesthesiol Scand. 2026 Oct;70(9):e70336. doi: 10.1111/aas.70336.
PubMed 42760033Mortensen CB, Andersen-Ranberg NC, Poulsen LM, Granholm A, Rasmussen BS, Kjaer MN, Lange T, Ebdrup BH, Collet MO, Andreasen AS, Bestle MH, Uslu B, Pedersen HS, Nielsen LG, Hastbacka J, Jensen TB, Damgaard K, Sommer T, Morgen M, Dey N, Citerio G, Estrup S, Egerod I, Samuelson K, Perner A, Mathiesen O. Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium. Intensive Care Med. 2024 Jan;50(1):103-113. doi: 10.1007/s00134-023-07282-7. Epub 2024 Jan 3.
PubMed 38170227Andersen-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.
PubMed 36286254
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Agents Intervening Against Delirium in Intensive Care Unit (AID-ICU) A Randomized, Blinded, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT03392376
- Acronym / sponsor ID
- AID-ICU / REG-169-2017
- Conditions
- Delirium
- Keywords
- ICU Delirium, Haloperidol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- 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)
- Study start
- 13 Jun 2018 (actual)
- Primary completion
- 9 Jul 2022 (actual)
- Study completion
- Jul 2023 (estimated)
- First posted
- 8 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Haloperidol injection | Experimental | Drug: Haloperidol InjectionHaloperidol 2,5mg x 3 daily, with additional as needed doses to a maximum of 20mg/daily. Other name: Serenase |
| Normal Saline | Placebo comparator | Other: Saline (0,9%)Saline (0,9%) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Acute admission to the ICU AND
- Age ≥ 18 years AND
- Diagnosed delirium with validated screening Tool as either CAM-ICU or ICDSC
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Haloperidol InjectionAlso: SerenaseICU 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. | Drug | Haloperidol injection |
| 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. | Other | Normal Saline |
Primary outcome
Days alive out of the hospital within 90 days post-randomization
Time frame: 90 days
Number of days alive and out of hospital
90-day mortality
Time frame: 90 days
Death from any cause within 90 days post-randomization
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
11 secondary outcomes
Number of days alive without delirium or coma in the ICU
Time frame: 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
Time frame: Measured every day from inclusion until ICU discharge, maximum 90 days
Usage of escape medicine
Time frame: Measured every day from inclusion until ICU discharge, maximum 90 days
Number of days alive without mechanical ventilation within 90 days postrandomisation
Time frame: Measured every day from inclusion until ICU discharge, maximum 90 days
Mortality
Time frame: 1 year
Quality of life (five level)
Time frame: 1 year
Quality of life (overall self assessment)
Time frame: 1 year
Cognitive function 1 year after randomisation at selected sites
Time frame: 1 year
Executive function 1 year after randomisation at selected sites
Time frame: 1 year
A health economic analysis
Time frame: 90 days
Cognitive function at admission
Time frame: At inclusion (within the first week)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2023.
- Derived from this study: PubMed 42760033Andersen-Ranberg NC, Poulsen LM, Perner A, Hastbacka J, Morgan M, Citerio G, Damby SE, Mortensen CB, Collet MO, Weber SO, Andreasen AS, Bestle M, Uslu B, Pedersen HS, Nielsen LG, Damgaard K, Jensen TB, Sommer T, Dey N, Mathiesen O, Granholm A. Haloperidol for Hypoactive and Hyperactive Delirium in ICU Patients-A Post Hoc Bayesian Analysis of the AID-ICU Trial. Acta Anaesthesiol Scand. 2026 Oct;70(9):e70336. doi: 10.1111/aas.70336.
- Derived from this study: PubMed 38170227Mortensen CB, Andersen-Ranberg NC, Poulsen LM, Granholm A, Rasmussen BS, Kjaer MN, Lange T, Ebdrup BH, Collet MO, Andreasen AS, Bestle MH, Uslu B, Pedersen HS, Nielsen LG, Hastbacka J, Jensen TB, Damgaard K, Sommer T, Morgen M, Dey N, Citerio G, Estrup S, Egerod I, Samuelson K, Perner A, Mathiesen O. Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium. Intensive Care Med. 2024 Jan;50(1):103-113. doi: 10.1007/s00134-023-07282-7. Epub 2024 Jan 3.
- Derived from this study: PubMed 36286254Andersen-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.
- LINK to the AID-ICU webpageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Delirium
RecruitingObservational study
The Impact of Fast-Track Anesthesia on Postoperative Neurocognitive Function in Patients Undergoing Cardiac Surgery
Delirium - Postoperative, Cardiac Surgery
Not yet recruiting
Prediction and Prevention of Postoperative Mortality and Morbidity
Dementia, Postoperative Delirium (POD)
Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
Out-Of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome
RecruitingPhase 3
Lactium Premedication to Prevent Emergence Agitation
Lactium, Premedication
Not yet recruiting
DEXmedetomidine for Postoperative Analgesia and Delirium Prevention After NEUROsurgery (DEX-NEURO Trial)
Neurosurgery, Brain Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
OIe Mathiesen, MD, PhD study chair
Zealand University Hospital
Anders Perner, MD,PhD study chair
Copenhagen University Hospital, Rigshospitalet
Jørn Wetterslev, MD, PhD study chair
Copenhagen Trial Unit, Center for Clinical Intervention Research
16 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Haloperidol Injection and Saline (0,9%) in people with Delirium, run by Zealand University Hospital at 16 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Denmark, Finland, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days alive out of the hospital within 90 days post-randomization (time frame: 90 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03392376, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2023.