The online version of this article (doi:10.1186/1471-2318-14-96) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
EJMS, OJV, PMB, and PWN conceived of the study and drafted the study protocol. EJMS, OJV, AV, KG, PMB, AMK, SHAD, SA, AS, EK, AML, RJM, AMS, LB, DP, MHHK, and PWBN participate in the design and coordination of the study. EJMS, AV, and KG support the data collection. PWBN has overall responsibility for the trial. EJMS, OJV, PMV, and PWBN performed the statistical analysis for the study protocol and the manuscript, and will primarily be responsible for interpretation of the study results and primary data analysis. EJMS drafted and revised the manuscript. OJV, PMV, PWBN critically revised the manuscript for important intellectual content. All authors have read and approved the final manuscript.
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).
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.
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.
American Psychiatric Association: Practice guideline for the treatment of patients with delirium. Am J Psychiatry. 1999, 156: 1-20. CrossRef
Kaneko T, Cai J, Ishikura T, Kobayashi M, Naka T, Kaibara N: Prophylactic consecutive administration of haloperidol can reduce the occurrence of postoperative delirium in gastrointestinal surgery. Yonago Acta Medica. 1999, 42: 179-184.
Kalisvaart KJ, de Jonghe JFM, Bogaards MJ, Vreeswijk R, Egberts TCG, Burger BJ, Eikelenboom P, van Gool WA: Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. 2005, 53: 1658-1666. 10.1111/j.1532-5415.2005.53503.x. CrossRefPubMed
Dutch Hospital Patient Safety Program (VMS Veiligheidsprogramma). http://www.vmszorg.nl/,
World Health Organization: International Statistical Classification of Diseases (ICD) and Related Health Problems, 10th Revision. 2010, Geneva: World Health Organization, ISBN 978-92-4-154834-2
WHO Collaborating Centre for Drug Statistics Methodology: Guidelines for ATC classification and DDD assignment 2013. 2012, Oslo: WHO Collaborating Centre for Drug Statistics Methodology, ISBN 978-82-8082-525-4
Maneeton B, Maneeton N, Srisurapanont M, Chittawatanarat K: Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial. Drug Des Dev Ther. 2013, 7: 657-667. CrossRef
Nakamura J, Uchimura N, Yamada S, Nakazawa Y: Does plasma free-3-methoxy-4-hydroxyphenyl(ethylene)glycol increase in the delirious state? A comparison of the effects of mianserin and haloperidol on delirium. Int Clin Psychopharmacol. 1997, 12: 147-152. 10.1097/00004850-199705000-00005. CrossRefPubMed
Donders E, Tillemans M, Vreeswijk R, Grootendorst D, Kalisvaart K: Effect of haloperidol dosing frequencies on the duration and severity of delirium in elderly hip fracture patients. A prospective randomized trial. Eur Geriatr Med. 2012, 3: S118-S119. CrossRef
Warren SR, Raisch DW, Campbell HM, Guarino PD, Kaufman JS, Petrokaitis E, Goldfarb DS, Gaziano JM, Jamison RL: Medication adherence assessment in a clinical trial with centralized follow-up and direct-to-patient drug shipments. Clin Trials. 2013, 10: 441-448. 10.1177/1740774511410331. CrossRefPubMed
Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, Philippides GJ, Roden DM, Zareba W: Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 2010, 55: 934-947. 10.1016/j.jacc.2010.01.001. CrossRefPubMedPubMedCentral
Drew BJ, Califf RM, Funk M, Kaufman ES, Krucoff MW, Laks MM, Macfarlane PW, Sommargren C, Swiryn S, Van Hare GF: Practice standards for electrocardiographic monitoring in hospital settings: an American Heart Association scientific statement from the Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Computerized Electrocardiology and the American Association of Critical-Care Nurses. Circulation. 2004, 110: 2721-2746. 10.1161/01.CIR.0000145144.56673.59. CrossRefPubMed
Goldberger JJ, Cain ME, Hohnloser SH, Kadish AH, Knight BP, Lauer MS, Maron BJ, Page RL, Passman RS, Siscovick D, Stevenson WG, Zipes DP: American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society Scientific Statement on Noninvasive Risk Stratification Techniques for Identifying Patients at Risk for Sudden Cardiac Death. A scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. J Am Coll Cardiol. 2008, 52: 1179-1199. 10.1016/j.jacc.2008.05.003. CrossRefPubMed
- 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 Schrijver
Oscar J de Vries
Karola de Graaf
Pierre M Bet
Peter M van de Ven
Ad M Kamper
Sabine HA Diepeveen
Anne M Lagaay
Rob J van Marum
Astrid M van Strien
Mark HH Kramer
Prabath WB Nanayakkara
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II