Haloperidol Prophylaxis in Older Emergency Department Patients

NCT01530308 | Completed Phase 4 DMC

• 3 other identifiers: NL38027.029.122011-004762-153207
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 6

Brief Summary

The investigators propose a multicenter, randomized, double-blinded, placebo-controlled trial to study the effect of additive low-dose haloperidol prophylaxis on top of exciting care in a general population of older patients (age 70 years and over) acutely admitted to the hospital through the emergency department (ED) for general medicine and surgical specialties, and who are at-risk for developing in-hospital delirium on admission according to the VMS delirium risk questions (one or more positive answers out of three questions). The investigators hypothesize that this intervention will reduce the incidence of in-hospital delirium as well as duration and severity of delirium.

Conditions

Delirium

Keywords

Delirium

Outcome Measures

Primary Outcomes (1)

• The initial day and number of days there is a significant change from baseline in the mean Delirium Observation Screening (DOS) score, and/or delirium is diagnosed according to the DSM-IV criteria.

  Reflecting the incidence, duration and severity of in-hospital delirium, which is the number of days in-hospital delirium is present in each participant who developed documented in-hospital delirium. Delirium symptoms are observed according to a mean Delirium Observation Screening (DOS) score \>3 out of three DOS scale scores/24 hours (indicating significant change), and diagnosed according to meeting the DSM-IV delirium criteria.

  Assessed within 1 to 7 days after initiation of the study intervention.

Secondary Outcomes (10)

• The number of days before there is a significant change from baseline in the mean Delirium Observation Screening (DOS) score, and delirium is diagnosed according to the DSM-IV delirium criteria.

  Assessed from 1st day of inclusion, during the 7-day intervention period, up to delirium diagnosis or hospital discharge.

• The (mean) number of days subjects are admitted to the hospital.

  Assessed from 1st day of admission up to hospital discharge.

• Functionality at baseline according to the Index of Independence in Activities of Daily Living (ADL)

  1 day of hospital admission.

• Change from baseline functionality at 3 months according to the Index of Independence in Activities of Daily Living (ADL)

  From baseline to assessment at time point 90 days after discharge date.

• Change from baseline functionality at 6 months according to the Index of Independence in Activities of Daily Living (ADL).

  From baseline to assessment at 180 days after discharge date.

Study Arms (2)

Investigational medicinal product

ACTIVE COMPARATOR

Haloperidol 1 mg twice daily at 12am and 20pm

Drug: Haloperidol

Placebo group

PLACEBO COMPARATOR

Placebo 1 mg twice daily at 12am and 20pm

Drug: Placebo

Interventions

Haloperidol DRUG

An oral dosage of 1mg twice daily at 12am and 8pm.

Also known as: Haldol, Antipsychotic agent, Dopamine antagonist, Butyrophenone

Investigational medicinal product

Placebo DRUG

An oral dosage of 1mg twice-daily at 12am and 8 pm.

Placebo group

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients aged 70 years or over;
• The patient is at increased risk for developing in-hospital delirium on admission according to one or more positive answers on the VMS delirium-risk questions;
• The patient and/or proxy is able to provide written informed consent;
• The patient and/or proxy speaks either Dutch or English;
• The patient is admitted to the hospital for a general medicine or surgical specialty.

You may not qualify if:

• Patients presenting in the ED with delirium according to the DSM-IV criteria;
• Patients with clinically significant (cardiac) disorders: QTc interval prolongation (QTc ≥500ms), recent acute myocardial infarction, uncompensated heart failure (working diagnosis), acute coronary syndrome (ACS), arrhythmias treated with class IA and III antiarrhythmic medicinal products, history of ventricular arrhythmia, history of torsades, clinically significant bradycardia, second or third degree heart block, uncorrected hypokalaemia (potassium level 3.0 or lower);
• Patients with vascular dementia;
• Patients with Lewy Body dementia;
• Patients with Parkinson dementia;
• Patients with (a history of) hypokinetic movement disorders;
• Patients with (a history of) malignant neuroleptic syndrome;
• Patients with (a history of) serotonergic syndrome;
• Patients with (a history of) central anticholinergic syndrome;
• Patients who will be admitted to the oncology ward;
• Patients previously enrolled in the HARPOON study, or in other medical- or drug studies;
• Patients using QT prolonging drugs and/or medications of which concomitant use with haloperidol is contraindicated (clinically relevant drug interactions, 1st degree, listed in the appendix of the study protocol);
• Epilepsy;
• Substance abuse and dependence (DSM-IV criteria)
• Patients who are not able to take the study medication according to protocol (amendment)

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (6)

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, North Brabant, 5223 GZ, Netherlands

Location

VUmc

Amsterdam, North Holland, 1007 MB, Netherlands

Location

Spaarne Ziekenhuis

Hoofddorp, North Holland, 2134 TM, Netherlands

Location

Medical Center Alkmaar

Alkmaar, Netherlands

Location

Rijnland Ziekenhuis

Leiderdorp, 2353 GA, Netherlands

Location

Isala Klinieken

Zwolle, 8011 JW, Netherlands

Location

Related Publications (1)

• Schrijver EJ, de Vries OJ, Verburg A, de Graaf K, Bet PM, van de Ven PM, Kamper AM, Diepeveen SH, Anten S, Siegel A, Kuiperi E, Lagaay AM, van Marum RJ, van Strien AM, Boelaarts L, Pons D, Kramer MH, Nanayakkara PW. Efficacy and safety of haloperidol prophylaxis for delirium prevention in older medical and surgical at-risk patients acutely admitted to hospital through the emergency department: study protocol of a multicenter, randomised, double-blind, placebo-controlled clinical trial. BMC Geriatr. 2014 Aug 28;14:96. doi: 10.1186/1471-2318-14-96.

  PMID: 25168927 DERIVED

MeSH Terms

Conditions

Delirium

Interventions

Haloperidol; Antipsychotic Agents; Dopamine Antagonists; Butyrophenones

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)

Ketones; Organic Chemicals; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Psychotropic Drugs; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action

Study Officials

• P WB Nanayakkara, Md, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• O J de Vries, MD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• P M Bet, Pharm D

  Amsterdam UMC, location VUmc

  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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: February 9, 2012
• Study Start: November 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: October 1, 2015
• Last Updated: November 26, 2015

Record last verified: 2015-11

Locations

NL (6)