pRophylactic halopEriDol Use for Delirium in iCu patiEnts With a High Risk for Delirium (REDUCE)

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ClinicalTrials.gov Identifier: NCT01785290

Recruitment Status : Completed

First Posted : February 7, 2013

Last Update Posted : April 17, 2017

Sponsor:

Collaborator:

ZonMw: The Netherlands Organisation for Health Research and Development

Information provided by (Responsible Party):

Radboud University

Study Description

Brief Summary:

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

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Study Design

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium

Drug Information available for: Haloperidol Haloperidol decanoate

U.S. FDA Resources

Arms and Interventions

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: aged ≥ 80 years weight ≤ 50 kg liver failure 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: aged ≥ 80 years weight ≤ 50 kg liver failure 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%

Outcome Measures

Primary Outcome Measures :

All cause mortality [ Time Frame: 28-day ]
Number of days of survival in 28-days after inclusion.

Secondary Outcome Measures :

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

Other Outcome Measures:

Quality of Life [ Time Frame: Baseline, 1 and 6 months ]
Efficacy of preventive haloperidol treatment on quality of life 1 and 6 months following ICU admission compared with baseline measurement

Eligibility Criteria

Information from the National Library of Medicine

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

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

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

Locations

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Netherlands
Radboud University Medical Centre
Nijmegen, Netherlands, 6500HB

Sponsors and Collaborators

Radboud University

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

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Principal Investigator:	Mark van den Boogaard, PhD	Radboud University Nijmegen Medical Centre, Dept of Intensive Care Medicine

More Information

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

van den Boogaard M, Slooter AJC, Brüggemann RJM, Schoonhoven L, Beishuizen A, Vermeijden JW, Pretorius D, de Koning J, Simons KS, Dennesen PJW, Van der Voort PHJ, Houterman S, van der Hoeven JG, Pickkers P; REDUCE Study Investigators, van der Woude MCE, Besselink A, Hofstra LS, Spronk PE, van den Bergh W, Donker DW, Fuchs M, Karakus A, Koeman M, van Duijnhoven M, Hannink G. Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium: The REDUCE Randomized Clinical Trial. JAMA. 2018 Feb 20;319(7):680-690. doi: 10.1001/jama.2018.0160. Erratum in: JAMA. 2018 Apr 10;319(14):1510.

van den Boogaard M, Slooter AJ, Brüggemann RJ, Schoonhoven L, Kuiper MA, van der Voort PH, Hoogendoorn ME, Beishuizen A, Schouten JA, Spronk PE, Houterman S, van der Hoeven JG, Pickkers P. Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial. Trials. 2013 Nov 21;14:400. doi: 10.1186/1745-6215-14-400.

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Responsible Party:	Radboud University
ClinicalTrials.gov Identifier:	NCT01785290 History of Changes
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:	April 17, 2017
Last Verified:	December 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Radboud University:


Delirium Survival Side-effects QoL

Additional relevant MeSH terms:

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Delirium Confusion Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Signs and Symptoms 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

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