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

This study has been completed.
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01785290
First received: January 31, 2013
Last updated: April 13, 2017
Last verified: December 2015
  Purpose

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 Intervention Phase
Delirium Drug: Haloperidol 1 mg/q8h Drug: Haloperidol 2 mg/q8h Drug: Placebo Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Radboud University:

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


Enrollment: 1800
Actual Study Start Date: June 2013
Study Completion Date: March 2017
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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%

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01785290

Locations
Netherlands
Radboud University Medical Centre
Nijmegen, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
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):
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 )
Study First Received: January 31, 2013
Last Updated: April 13, 2017
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:
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

ClinicalTrials.gov processed this record on July 26, 2017