pRophylactic halopEriDol Use for Delirium in iCu patiEnts With a High Risk for Delirium (REDUCE)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01785290 |
Recruitment Status :
Completed
First Posted : February 7, 2013
Last Update Posted : November 12, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
The aim of this study is to determine the effects of a low dosage of prophylactic haloperidol in patients with a high risk to develop delirium, defined by an expected ICU length of stay of >1 day. The investigators hypothesized that haloperidol prophylaxis in patients with a high risk for delirium reduces 28-day mortality, delirium and delirium related outcome.
Two different dosages of haloperidol are used in this study to compare with placebo. A dosage of 1mg, or 2mg or placebo three times a day in a double-blinded fashion resulting in a three-armed multicentre randomized double-blinded placebo-controlled trial. To relate the potential beneficial effects of haloperidol to the a priori risk to develop delirium, the PREDELIRIC-model (delirium prediction model for ICU patients) will be used. This will enable the investigators to determine the preventive efficacy of haloperidol in patient groups based on their risk to develop delirium.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Delirium | Drug: Haloperidol 1 mg/q8h Drug: Haloperidol 2 mg/q8h Drug: Placebo | Phase 4 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 1800 participants |
Allocation: | Randomized |
Intervention Model: | Single Group Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Prevention |
Official Title: | Prophylactic Haloperidol Use for Delirium in ICU Patients; a Randomized Placebo-controlled Double-blind Multicentre Trial |
Actual Study Start Date : | June 2013 |
Actual Primary Completion Date : | December 2016 |
Actual Study Completion Date : | March 2017 |
Arm | Intervention/treatment |
---|---|
Experimental: Haloperidol 1mg/q8h
Prophylactic haloperidol of 1 mg/q8h i.v.
|
Drug: Haloperidol 1 mg/q8h
Patients receive prophylactic haloperidol until discharge from the ICU or when delirium occurs. In the latter case study drug will be stopped and patients will be subsequently treated according to the delirium protocol with open-label haloperidol. To avoid unnecessary risk for side-effects the dose will be halved in patients:
Patients with an adjusted dosage of study drug remain allocated to their original group. In case of occurrence of QTc-time prolongation the study drug will be stopped. After normalisation of QTc-time (<500msec.) the study drug will be restarted. If QTc-time becomes prolonged again, the study drug will be stopped definitively. The patient will remain allocated to the original study group. Other Name: Haldol |
Experimental: Haloperidol 2mg/q8h
Prophylactic haloperidol 2mg/q8h i.v.
|
Drug: Haloperidol 2 mg/q8h
Patients receive prophylactic haloperidol until discharge from the ICU or when delirium occurs. In the latter case study drug will be stopped and patients will be subsequently treated according to the delirium protocol with open-label haloperidol. To avoid unnecessary risk for side-effects the dose will be halved in patients:
Patients with an adjusted dosage of study drug remain allocated to their original group. In case of occurrence of QTc-time prolongation the study drug will be stopped. After normalisation of QTc-time (<500msec.) the study drug will be restarted. If QTc-time becomes prolonged again, the study drug will be stopped definitively. The patient will remain allocated to the original study group. Other Name: Haldol |
Placebo Comparator: Sodium chloride 0.9%
Placebo (Sodium chloride 0.9%) three times a day
|
Drug: Placebo
Sodium Chloride 0.9%
Other Name: Sodium Chloride 0.9% |
- All cause mortality [ Time Frame: 28-day ]Number of days of survival in 28-days after inclusion.
- Delirium incidence during ICU stay [ Time Frame: up to 28 days ]The onset of delirium during ICU admission
- Number of delirium free days [ Time Frame: 28 days ]Number of delirium and coma-free days in 28 days
- Delirium related outcome during ICU stay [ Time Frame: up to 28 days ]Time to successful extubation, incidence of re-intubation, incidence of ICU readmission, and incidence of unplanned removal of tubes and catheters during period of 28-days after inclusion of study, use of physical restraints
- Determining efficacy in different risk groups [ Time Frame: up to 28 days ]Determine the preventive efficacy of haloperidol in different patient groups based on the a priori risk to develop delirium: In patients with a predicted risk up to 50%, 50-70%, 70-90%, above 90% the effect of haloperidol will be determined
- Side effects of haloperidol prophylaxis during prophylactic treatment [ Time Frame: up to 28 days ]Evaluating the incidence of known side effects of haloperidol during the prophylactic treatment period
- All cause mortality [ Time Frame: 90 day ]Number of days of survival in 90-days after inclusion, survival analysis stratifying for delirium incidence will be performed

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- age ≥ 18
- expected length of ICU stay of over one day
Exclusion Criteria:
- history of epilepsy, Parkinson's disease, hypokinetic rigid syndrome, dementia or alcohol withdrawal syndrome
- patients admitted to the ICU for neurological reasons (including post-resuscitation patients)
- patients treated with other anti-psychotics
- prolonged QTc-time (>500msec) or history of serious ventricular arrhythmia (in last 12 months)
- pregnancy/breast feeding
- delirious before ICU admission
- serious auditory or visual disorders
- ICU-stay ≤1 day
- unable to understand Dutch
- severely mentally disabled
- serious receptive aphasia
- moribund and not expected to survive 2 days
- known allergy to haloperidol

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01785290
Netherlands | |
Radboud University Medical Centre | |
Nijmegen, Netherlands, 6500HB |
Principal Investigator: | Mark van den Boogaard, PhD | Radboud University Nijmegen Medical Centre, Dept of Intensive Care Medicine |
Responsible Party: | Radboud University Medical Center |
ClinicalTrials.gov Identifier: | NCT01785290 |
Other Study ID Numbers: |
Delirium_Haldol-prophy 2012-004012-66 ( EudraCT Number ) 2012/424 ( Other Identifier: Medical Ethical Committee of Arnhem-Nijmegen ) |
First Posted: | February 7, 2013 Key Record Dates |
Last Update Posted: | November 12, 2020 |
Last Verified: | December 2015 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | on request available |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) |
Time Frame: | available on request |
Access Criteria: | on request |
Delirium Survival Side-effects QoL |
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 |