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What is the primary objective of this study?

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.

Who is eligible to participate?

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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Delirium

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Haloperidol 1 mg/q8hPatients 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.

Drug:Haloperidol 2 mg/q8hPatients 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.

Drug:PlaceboSodium Chloride 0.9%

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Haloperidol 1mg/q8hProphylactic haloperidol of 1 mg/q8h i.v.

Haloperidol 2mg/q8hProphylactic haloperidol 2mg/q8h i.v.

Sodium chloride 0.9%Placebo (Sodium chloride 0.9%) three times a day

Study Status

Completed

Start Date: June 2013

Completed Date: March 2017

Phase: Phase 4

Type: Interventional

Design:

Primary Outcome: All cause mortality

Secondary Outcome: Delirium incidence during ICU stay

Study sponsors, principal investigator, and references

Principal Investigator: Mark van den Boogaard, PhD

Lead Sponsor: Radboud University

Collaborator: ZonMw: The Netherlands Organisation for Health Research and Development

More information:https://clinicaltrials.gov/show/NCT01785290