Efficacy of Haloperidol to Decrease the Burden of Delirium in Adult Critically Ill Patients (EuRIDICE): a Prospective Randomised Multi-center Double-blind Placebo-controlled Clinical Trial
Overview
- Phase
- Phase 3
- Intervention
- Haloperidol
- Conditions
- Delirium
- Sponsor
- Erasmus Medical Center
- Enrollment
- 142
- Locations
- 8
- Primary Endpoint
- delirium- and coma-free days
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
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.
Detailed Description
BACKGROUND. Although widely used, the efficacy and safety of haloperidol for delirium in critically ill adults remain unclear. A randomised controlled trial is warranted to study the effect of haloperidol on delirium or coma, long-term outcomes, safety concerns, and cost-effectiveness. SUMMARY. The investigators will perform a multi-center, randomised, double-blind, placebo-controlled clinical trial to evaluate the use of haloperidol for delirium treatment in 742 critically ill adults with delirium. Days spent without delirium- or coma in the first 14 days after randomisation is the primary outcome. Study drug will be initiated at 2.5mg IV q8h and increased after 24 hours to 5mg IV q8h if delirium persists. Study drug dose will be tapered when delirium has resolved during 24 hours. All patients will be managed with a standardized pain, agitation and delirium protocol. Standard operating procedures for agitation (analgesia titration, alpha2 agonists) and hallucination management (atypical antipsychotics) will be implemented to accommodate possible imbalances of these symptoms in both treatment arms. Open-label haloperidol administration is discouraged during the trial. The sample size provides a power of 90% to detect statistically significant results (p\<.05) and a true treatment difference of one day for the primary outcome between trial arms. This trial is expected to answer the clinically relevant question whether haloperidol still deserves a place in ICU delirium management. The primary outcome (delirium- and coma-free days) will be related to the secondary outcomes cognitive dysfunction, functional and psychological outcomes and patient- and family experiences. An extensive cost-effectiveness analysis will be done. Mortality at one year and safety concerns of haloperidol (QTc prolongation on EKG and rigidity) will be assessed as secondary endpoints. In conclusion, this large multicentre trial will assess efficacy and safety of haloperidol for ICU delirium.
Investigators
Mathieu van der Jagt
Principal Investigator / Medical Doctor, PhD
Erasmus Medical Center
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
haloperidol
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).
Intervention: Haloperidol
placebo
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).
Intervention: Placebo
Outcomes
Primary Outcomes
delirium- and coma-free days
Time Frame: within the first 14 days after randomisation
days without brain dysfunction (=delirium OR coma) while at the ICU
Secondary Outcomes
- Cognitive deterioration: Cognitive flexibility(3 and 12 months)
- mortality(28 days and 1 year)
- Patients' and family-members' experiences related to delirium(at discharge from hospital (up to a maximum of 12 months after randomisation = end of follow-up period) and 3 months after randomisation)
- Cognitive deterioration: Semantic fluency(3 and 12 months)
- length of stay at ICU(days of ICU stay (time in days from ICU admission until ICU discharge). Assessed up to a maximum of 12 months after randomisation (end of follow-up period).)
- Adverse drug associated events: prolonged QTc by EKG(while on study drug treatment during study period at ICU (up to 14 days after randomisation))
- Cognitive deterioration: Global cognitive functioning(3 and 12 months)
- Cognitive deterioration: Working memory(3 and 12 months)
- Cognitive deterioration: Word retrieval(3 and 12 months)
- Anxiety and depression(3 and 12 months)
- Adverse drug associated events: ventricular arrhythmia's(during study period at ICU (up to 14 days after randomisation))
- Functional outcome(3 and 12 months)
- Adverse drug associated events: muscle rigidity and other associated movements disorders(while on study drug treatment during study period at ICU (up to 14 days after randomisation))
- Cognitive deterioration: Verbal learning and memory(3 and 12 months)
- Patients' memories related to their ICU stay(at discharge from hospital (up to a maximum of 12 months after randomisation = end of follow-up period) and 3 months after randomisation)
- Posttraumatic stress syndrome(at 3 months after randomisation)
- Caregiver Strain(at 3 months after randomisation)