Effects of Prophylactic Use of Haloperidol in Critically Ill Patients With a High Risk for Delirium

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Radboud University
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: July 23, 2014
Last verified: July 2014
  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
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effects of Prophylactic Use of Haloperidol in Critically Ill Patients With a High Risk for Delirium; 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 ] [ Designated as safety issue: Yes ]
    Number of days of survival in 28-days after inclusion.


Secondary Outcome Measures:
  • Delirium incidence during ICU stay [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]
    The onset of delirium during ICU admission

  • Number of delirium free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Number of delirium and coma-free days in 28 days

  • Delirium related outcome during ICU stay [ Time Frame: up to 28 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Evaluating the incidence of known side effects of haloperidol during the prophylactic treatment period

  • All cause mortality [ Time Frame: 90 day ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Efficacy of preventive haloperidol treatment on quality of life 1 and 6 months following ICU admission compared with baseline measurement


Estimated Enrollment: 2145
Study Start Date: June 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: December 2015 (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

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

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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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

Contacts
Contact: Mark van den Boogaard, PhD 0031243665009 Mark.vandenBoogaard@radboudumc.nl
Contact: Peter Pickkers, MD, PhD 0031243615363 Peter.Pickkers@radboudumc.nl

Locations
Netherlands
Radboud University Medical Centre Recruiting
Nijmegen, Netherlands, 6500HB
Contact: Mark van den Boogaard, PhD    0031243665009    Mark.vandenBoogaard@radboudumc.nl   
Contact: Peter Pickkers, MD, PhD    0031243615363    Peter.Pickkers@radboudumc.nl   
Principal Investigator: Mark van den Boogaard, PhD         
Principal Investigator: Peter Pickkers, MD, PhD         
Sub-Investigator: Johannes G. van der Hoeven, MD, PhD         
Sub-Investigator: Arjen Slooter, MD, PhD         
Sponsors and Collaborators
Radboud University
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: Peter Pickkers, MD, PhD Radboud University Nijmegen Medical Centre, Dept of Intensive Care Medicine
  More Information

No publications provided by Radboud University

Additional 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, 2012/424
Study First Received: January 31, 2013
Last Updated: July 23, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Delirium
Survival
Side-effects
QoL

Additional relevant MeSH terms:
Delirium
Delirium, Dementia, Amnestic, Cognitive Disorders
Critical Illness
Disease Attributes
Pathologic Processes
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Mental Disorders
Haloperidol
Haloperidol decanoate
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
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 August 28, 2014