Open Access Study protocol

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

Edmée JM Schrijver1*, Oscar J de Vries12, Astrid Verburg12, Karola de Graaf1, Pierre M Bet3, Peter M van de Ven4, Ad M Kamper5, Sabine HA Diepeveen6, Sander Anten7, Andrea Siegel7, Esther Kuipéri78, Anne M Lagaay9, Rob J van Marum10, Astrid M van Strien10, Leo Boelaarts11, Douwe Pons11, Mark HH Kramer1 and Prabath WB Nanayakkara112

Author Affiliations

1 Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

2 Section of Geriatrics, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

3 Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands

4 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

5 Section of Geriatrics, Department of Internal Medicine, Isala Hospital, Zwolle, The Netherlands

6 Section of Acute Medicine, Department of Internal Medicine, Isala Hospital, Zwolle, The Netherlands

7 Department of Internal Medicine, Rijnland Hospital, Leiderdorp, The Netherlands

8 Currently: specialist training in General Practice at Leiden University Medical Center, Leiden, The Netherlands

9 Section of Geriatrics, Department of Internal Medicine, Spaarne Hospital, Hoofddorp, The Netherlands

10 Department of Geriatric Medicine, Jeroen Bosch Hospital, ’s Hertogenbosch, The Netherlands

11 Department of Geriatric Medicine, Medical Centre Alkmaar, Alkmaar, The Netherlands

12 Section of Acute Medicine, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

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BMC Geriatrics 2014, 14:96  doi:10.1186/1471-2318-14-96

Published: 28 August 2014

Abstract

Background

Delirium is associated with substantial morbidity and mortality rates in elderly hospitalised patients, and a growing problem due to increase in life expectancy. Implementation of standardised non-pharmacological delirium prevention strategies is challenging and adherence remains low. Pharmacological delirium prevention with haloperidol, currently the drug of choice for delirium, seems promising. However, the generalisability of randomised controlled trial results is questionable since studies have only been performed in selected postoperative hip-surgery and intensive care unit patient populations. We therefore present the design of the multicenter, randomised, double-blind, placebo-controlled clinical trial on early pharmacological intervention to prevent delirium: haloperidol prophylaxis in older emergency department patients (The HARPOON study).

Methods/Design

In six Dutch hospitals, at-risk patients aged 70 years or older acutely admitted through the emergency department for general medicine and surgical specialties are randomised (n = 390) for treatment with prophylactic haloperidol 1 mg or placebo twice daily for a maximum of seven consecutive days. Primary outcome measure is the incidence of in-hospital delirium within seven days of start of the study intervention, diagnosed with the Confusion Assessment Method, and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for delirium. Secondary outcome measures include delirium severity and duration assessed with the Delirium Rating Scale Revised 98; number of delirium-free days; adverse events; hospital length-of-stay; all-cause mortality; new institutionalisation; (Instrumental) Activities of Daily Living assessed with the Katz Index of ADL, and Lawton IADL scale; cognitive function assessed with the Six-item Cognitive Impairment Test, and the Dutch short form Informant Questionnaire on Cognitive Decline in the Elderly. Patients will be contacted by telephone three and six months post-discharge to collect data on cognitive- and physical function, home residency, all-cause hospital admissions, and all-cause mortality.

Discussion

The HARPOON study will provide relevant information on the efficacy and safety of prophylactic haloperidol treatment for in-hospital delirium and its effects on relevant clinical outcomes in elderly at-risk medical and surgical patients.

Trial registration

EudraCT Number: 201100476215; ClinicalTrials.gov Identifier: NCT01530308; Dutch Clinical Trial Registry: NTR3207

Keywords:
Haloperidol; Delirium; Prophylactic treatment; Older patients