Haloperidol for Delirium in Adult Critically Ill Patients

NCT03628391 | Terminated Phase 3 DMC

• 1 other identifier: MEC-2017-115/NL62689.078.17
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 8

Brief Summary

The EuRIDICE trial will study whether haloperidol as a first line treatment for ICU delirium reduces delirium duration (and severity). Adverse outcomes typically associated with delirium will also be studied and include long term cognition, functional outcome and quality of life. Further, patient and family experiences and cost-effectiveness will be assessed. Finally, safety concerns associated with the use of haloperidol in this vulnerable population will be studied.

Conditions

Delirium; Critical Illness; Intensive Care Psychosis; Cognitive Impairment; Cognitive Decline

Keywords

delirium; intensive care unit; critical illness; cognitive impairment

Outcome Measures

Primary Outcomes (1)

• delirium- and coma-free days

  days without brain dysfunction (=delirium OR coma) while at the ICU

  within the first 14 days after randomisation

Secondary Outcomes (17)

• Cognitive deterioration: Global cognitive functioning

  3 and 12 months

• Cognitive deterioration: Verbal learning and memory

  3 and 12 months

• Cognitive deterioration: Semantic fluency

  3 and 12 months

• Cognitive deterioration: Working memory

  3 and 12 months

• Cognitive deterioration: Cognitive flexibility

  3 and 12 months

Study Arms (2)

haloperidol

ACTIVE COMPARATOR

study drug will be titrated based on delirium, diagnosed with a validated screening instrument (CAM-ICU or ICDSC), starting with 2.5mg IV q8h and titrated to a maximum of 5mg IV q8h. Agitation and hallucinations will be managed according to a pre-specified protocol in both treatment arms. First the study drug will be increased when agitation or delirium remain present. Further options include mainly the use of alfa-2 agonists (agitation) or atypical antipsychotic drugs (hallucinations).

Drug: Haloperidol

placebo

PLACEBO COMPARATOR

study drug will be titrated based on delirium, diagnosed with a validated screening instrument (CAM-ICU or ICDSC), starting with 2.5mg IV q8h and titrated to a maximum of 5mg IV q8h. Agitation and hallucinations will be managed according to a pre-specified protocol in both treatment arms. First the study drug will be increased when agitation or delirium remain present. Further options include mainly the use of alfa-2 agonists (agitation) or atypical antipsychotic drugs (hallucinations).

Drug: Placebo

Interventions

Haloperidol DRUG

haloperidol for ICU delirium, titrated on validated screening tool-based diagnosis

Also known as: not any

haloperidol

Placebo DRUG

placebo for ICU delirium, titrated on validated screening tool-based diagnosis

placebo

Eligibility Criteria

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

You may qualify if:

• Delirium, as assessed with the Intensive Care Delirium Screening Checklist - ICDSC: ≥4 or Confusion Assessment Method for the ICU - CAM-ICU: positive). NB Delirium can occur in the course of ICU admission or be present at admission.
• Written Informed Consent is obtained from patient or legal representative

You may not qualify if:

• Eligibility
• Age ≥ 18 years
• Admitted to ICU.
• Pregnancy (to be excluded by pregnancy test in women of child baring age)
• History of ventricular arrhythmia including "torsade de pointes" (TdP)
• Known allergy to haloperidol
• History of dementia or an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score ≥ 4
• History of malignant neuroleptic syndrome or parkinsonism (either Parkinson's disease or another hypokinetic rigid syndrome)
• Schizophrenia or other psychotic disorder
• Inability to conduct valid delirium screening assessment (e.g. coma, deaf, blind) or inability to speak Dutch
• The patient is expected to die within 24 hours, or is expected to leave the ICU within 24 hours after evaluation (may be reassessed daily)
• Prolonged QT-interval (QTc \> 500ms)
• (recent) "torsade de pointes" (TdP)
• (recent) malignant neuroleptic syndrome or parkinsonism
• Evidence of acute alcohol (or substance) withdrawal requiring pharmacological intervention (e.g. benzodiazepines or alfa-2 agonist) to treat

Sponsors & Collaborators

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

Study Sites (8)

Jeroen Bosch ziekenhuis

's-Hertogenbosch, Netherlands

Location

IJsselland Hospital

Capelle aan den IJssel, Netherlands

Location

Albert Schweitzer Hospital

Dordrecht, Netherlands

Location

Radboudumc

Nijmegen, Netherlands

Location

ErasmusMC

Rotterdam, Netherlands

Location

Franciscus Gasthuis (Hospital)

Rotterdam, Netherlands

Location

Ikazia Hospital

Rotterdam, Netherlands

Location

Maasstad Hospital

Rotterdam, Netherlands

Location

Related Publications (2)

• Smit L, Slooter AJC, Devlin JW, Trogrlic Z, Hunfeld NGM, Osse RJ, Ponssen HH, Brouwers AJBW, Schoonderbeek JF, Simons KS, van den Boogaard M, Lens JA, Boer DP, Gommers DAMPJ, Rietdijk WJR, van der Jagt M; EuRIDICE study group. Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial. Crit Care. 2023 Oct 30;27(1):413. doi: 10.1186/s13054-023-04692-3.

  PMID: 37904241 DERIVED

• Smit L, Trogrlic Z, Devlin JW, Osse RJ, Ponssen HH, Slooter AJC, Hunfeld NGM, Rietdijk WJR, Gommers D, van der Jagt M; EuRIDICE study group. Efficacy of halopeRIdol to decrease the burden of Delirium In adult Critically ill patiEnts (EuRIDICE): study protocol for a prospective randomised multi-centre double-blind placebo-controlled clinical trial in the Netherlands. BMJ Open. 2020 Sep 23;10(9):e036735. doi: 10.1136/bmjopen-2019-036735.

  PMID: 32967873 DERIVED

MeSH Terms

Conditions

Delirium; Critical Illness; Cognitive Dysfunction

Interventions

Haloperidol

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Cognition Disorders

Intervention Hierarchy (Ancestors)

Butyrophenones; Ketones; Organic Chemicals

Study Officials

• Mathieu van der Jagt, MD PhD

  Erasmus University Medical Center Rotterdam, The Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: placebo and haloperidol (verum) will have the same appearance
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator / Medical Doctor, PhD

Model Details: Randomised controlled double-blind placebo controlled clinical trial

Study Record Dates

• First Submitted: October 9, 2017
• First Posted: August 14, 2018
• Study Start: February 22, 2018
• Primary Completion: February 3, 2020
• Study Completion: January 23, 2021
• Last Updated: May 11, 2022

Record last verified: 2022-05

Locations

NL (8)