title: 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.
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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  EudraCT Number: 201100476215; ClinicalTrials.gov Identifier: NCT01530308; Dutch Clinical Trial Registry: NTR3207.
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands. ej.schrijver@vumc.nl.
authors.forename: Edmée J M
authors.initials: EJ
authors.lastname: Schrijver
authors.forename: Oscar J
authors.initials: OJ
authors.lastname: de Vries
authors.forename: Astrid
authors.initials: A
authors.lastname: Verburg
authors.forename: Karola
authors.initials: K
authors.lastname: de Graaf
authors.forename: Pierre M
authors.initials: PM
authors.lastname: Bet
authors.forename: Peter M
authors.initials: PM
authors.lastname: van de Ven
authors.forename: Ad M
authors.initials: AM
authors.lastname: Kamper
authors.forename: Sabine Ha
authors.initials: SH
authors.lastname: Diepeveen
authors.forename: Sander
authors.initials: S
authors.lastname: Anten
authors.forename: Andrea
authors.initials: A
authors.lastname: Siegel
authors.forename: Esther
authors.initials: E
authors.lastname: Kuipéri
authors.forename: Anne M
authors.initials: AM
authors.lastname: Lagaay
authors.forename: Rob J
authors.initials: RJ
authors.lastname: van Marum
authors.forename: Astrid M
authors.initials: AM
authors.lastname: van Strien
authors.forename: Leo
authors.initials: L
authors.lastname: Boelaarts
authors.forename: Douwe
authors.initials: D
authors.lastname: Pons
authors.forename: Mark H H
authors.initials: MH
authors.lastname: Kramer
authors.forename: Prabath W B
authors.initials: PW
authors.lastname: Nanayakkara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D003693:Delirium / Q000175:diagnosis / Q000517:prevention & control*; D004311:Double-Blind Method; D004636:Emergency Service, Hospital / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D006220:Haloperidol / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D010343:Patient Admission / Q000639:trends; D012307:Risk Factors; D013503:Surgery Department, Hospital / Q000639:trends; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D006220:Haloperidol