Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial

Nov 23, 2013Trials

Using haloperidol to prevent ICU delirium and related problems: plan for a large randomized trial

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

A total of 2,145 ICU patients will be randomized to assess the effects of haloperidol prophylaxis on 28-day survival.

The study aims to evaluate the impact of haloperidol prophylaxis on the incidence of delirium and related outcomes.
Two intervention groups will receive haloperidol at doses of 1 mg or 2 mg every 8 hours, while a control group will receive placebo.
An anticipated mortality rate of 12% in the placebo group sets the basis for the power calculations.
Haloperidol treatment will be halted for patients who develop delirium, after which they will receive higher therapeutic doses.
This multicenter trial is designed to provide robust evidence regarding the effectiveness of haloperidol in preventing delirium in critically ill patients.

AI simplified

BACKGROUND: Delirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis.

METHODS: This will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive non-neurological ICU patients, aged ≥ 18 years with an expected ICU length of stay >1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates.

DISCUSSION: This will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately powered to demonstrate an effect on 28-day survival.

TRIAL REGISTRATION: Clinicaltrials.gov: NCT01785290.EudraCT number: 2012-004012-66.

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View on DOI ↗View on PubMed ↗

Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief