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

NCT01785290 | Completed Phase 4 DMC

• 3 other identifiers: Delirium_Haldol-prophy2012-004012-662012/424
• Study Type: interventional
• Target: 1,800
• Locations: 1 country
• Sites: 1

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.

Conditions

Delirium

Keywords

Delirium; Survival; Side-effects; QoL

Outcome Measures

Primary Outcomes (1)

• All cause mortality

  Number of days of survival in 28-days after inclusion.

  28-day

Secondary Outcomes (6)

• Delirium incidence during ICU stay

  up to 28 days

• Number of delirium free days

  28 days

• Delirium related outcome during ICU stay

  up to 28 days

• Determining efficacy in different risk groups

  up to 28 days

• Side effects of haloperidol prophylaxis during prophylactic treatment

  up to 28 days

Study Arms (3)

Haloperidol 1mg/q8h

EXPERIMENTAL

Prophylactic haloperidol of 1 mg/q8h i.v.

Drug: Haloperidol 1 mg/q8h

Haloperidol 2mg/q8h

EXPERIMENTAL

Prophylactic haloperidol 2mg/q8h i.v.

Drug: Haloperidol 2 mg/q8h

Sodium chloride 0.9%

PLACEBO COMPARATOR

Placebo (Sodium chloride 0.9%) three times a day

Drug: Placebo

Interventions

Haloperidol 1 mg/q8h DRUG

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.

Also known as: Haldol

Haloperidol 1mg/q8h

Haloperidol 2 mg/q8h DRUG

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.

Also known as: Haldol

Haloperidol 2mg/q8h

Placebo DRUG

Sodium Chloride 0.9%

Also known as: Sodium Chloride 0.9%

Sodium chloride 0.9%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age ≥ 18
• expected length of ICU stay of over one day

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

Radboud University Medical Centre

Nijmegen, 6500HB, Netherlands

Location

Related Publications (4)

• Duprey MS, van den Boogaard M, van der Hoeven JG, Pickkers P, Briesacher BA, Saczynski JS, Griffith JL, Devlin JW. Association between incident delirium and 28- and 90-day mortality in critically ill adults: a secondary analysis. Crit Care. 2020 Apr 20;24(1):161. doi: 10.1186/s13054-020-02879-6.

  PMID: 32312288 DERIVED

• Heesakkers H, Devlin JW, Slooter AJC, van den Boogaard M. Association between delirium prediction scores and days spent with delirium. J Crit Care. 2020 Aug;58:6-9. doi: 10.1016/j.jcrc.2020.03.008. Epub 2020 Mar 25.

  PMID: 32247156 DERIVED

• van den Boogaard M, Slooter AJC, Bruggemann 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.

  PMID: 29466591 DERIVED

• van den Boogaard M, Slooter AJ, Bruggemann 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.

  PMID: 24261644 DERIVED

MeSH Terms

Conditions

Delirium

Interventions

Haloperidol; Sodium Chloride

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Butyrophenones; Ketones; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Mark van den Boogaard, PhD

  Radboud University Nijmegen Medical Centre, Dept of Intensive Care Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2013
• First Posted: February 7, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: March 1, 2017
• Last Updated: November 12, 2020

Record last verified: 2015-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: available on request
• Access Criteria: on request

Locations

NL (1)