PROfylactic Haloperidol in Patients Defined as High Risk for DElirium With Delirium Risk mOdel

Delirium Clinical Trial

— PRODEO  

Official title:

Delirium: Is Prophylactic Drug Therapy Useful in High Risk Patients as Defined by the Delirium Risk Prediction Model?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03199950
• Other study ID #: 17-T-31
• Secondary ID: 2017-001260-37
• Status: Recruiting
• Phase: Phase 4
• First received: June 23, 2017
• Last updated: June 26, 2017
• Start date: June 23, 2017
• Est. completion date: November 23, 2018

Study information

• Verified date: June 2017
• Source: Zuyderland Medisch Centrum
• Contact: Hugo van der Kuy
• Phone: 088 4595945
• Email: h.vanderkuy[@]zuyderland.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The hospital pharmacy at the Zuyderland Medical Centre developed the DElirium MOdel (DEMO) to predict which patients are at risk of developing a delirium in patients aged 60 or older. With this delirium risk prediction model we aim to predict more accurately which patients are at high risk of developing a delirium and want to investigate if these patients can benefit from prophylactic haloperidol.

Description:

Intro: Delirium is a common postoperative complication within geriatric patients. It is described delirium as a very stressful experience for the patient which can lead to prolonged hospital stay, higher cost, additional morbidity and increased mortality.

In 2013 the hospital pharmacy at the Zuyderland Medical Center developed the delirium risk prediction model to determine the chance of development of a delirium in patients aged 60 or older. Electronically available data such as age, polypharmacy, use of anti-dementia drugs, anti-depressants, anti-parkinsonian drugs, anti-diabetics, analgesics and/or sleeping medication were used in the study. The delirium risk prediction model was validated prospectively after retrospective development. The model will be used in this study to predict the risk of developing delirium postoperatively.

We expect prophylactic haloperidol to be effective in patients with a high risk of developing a delirium according to the delirium risk prediction model.

Aim: The PRODEO-study aims to reduce the incidence of postoperative delirium by administering prophylactic haloperidol to patients with a high risk of developing delirium according to the delirium risk prediction model.

Methods: The study is a randomized and double blind single center study with two parallel groups. Subjects ≥60 years with increased risk of postoperative delirium according to the delirium risk prediction model undergoing elective chirurgical or elective orthopedic surgery are eligible. Subjects will be excluded if they already use anti-psychotic drugs, are not able to take oral medication or when there are contra-indications. Haloperidol (1mg) or placebo will be administered at set times postoperatively. Subjects receive haloperidol 2dd1mg or a placebo 2dd during a maximum of five days during admission. On day 3 blood samples will be obtained in order to determine the true concentration levels of haloperidol. The primary endpoint is delirium incidence within 5 days after surgery. Secondary endpoints are costs of treatment, number of admission days, adverse events, true concentration levels of haloperidol and duration and severity of delirium.

Results: The study will start in June 2017 with an inclusion rate of 20 patients per week. An incidence reduction of 30% in the intervention group is expected. To reach sufficient statistical power a study population of 1366 subjects is needed. Duration of the inclusion period is expected to be 18 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1366
• Est. completion date: November 23, 2018
• Est. primary completion date: November 23, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion criteria

• Age >60 years

• Planned elective surgery

• General surgery or orthopaedic surgery

• At least one night postsurgical admission

• High-risk developing delirium according to the DEMO-model

• Absence of delirium pre-operatively

Exclusion criteria

• Less than 1-day postoperative admission in hospital

• Hypersensitivity to butyrophenone derivates

• Use of antipsychotics

• Not being able to take oral medication

• Presence of contraindications (lesions of basal ganglia, clinical significant heart disease (eg. recent acute myocardial infarction, non-compensated heart failure, arrythmias treated with drugs out of the NYHA(New York Heart Association)-class Ia and II anti-arrythmics), known prolongation of the QT interval, history of ventricular arrythmia and torsades de pointes, uncorrected hypokalemia.

Related Conditions & MeSH terms

• Delirium

Intervention

Drug:
• Haloperidol
Haloperidol 2dd1mg (08.00am - 10.00pm)
• Placebo Oral Tablet
Placebo oral 2dd (08.00am - 10.00pm)

Locations

Country	Name	City	State
Netherlands	Zuyderland Medisch Centrum	Sittard	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Zuyderland Medisch Centrum

Country where clinical trial is conducted

Netherlands, 

References & Publications (7)

de Wit HA, Winkens B, Mestres Gonzalvo C, Hurkens KP, Mulder WJ, Janknegt R, Verhey FR, van der Kuy PH, Schols JM. The development of an automated ward independent delirium risk prediction model. Int J Clin Pharm. 2016 Aug;38(4):915-23. doi: 10.1007/s11096-016-0312-7. Epub 2016 May 13. — View Citation

Demeure MJ, Fain MJ. The elderly surgical patient and postoperative delirium. J Am Coll Surg. 2006 Nov;203(5):752-7. Epub 2006 Sep 26. Erratum in: J Am Coll Surg. 2007 Jan;204(1):191. — View Citation

Fukata S, Kawabata Y, Fujisiro K, Katagawa Y, Kuroiwa K, Akiyama H, Terabe Y, Ando M, Kawamura T, Hattori H. Haloperidol prophylaxis does not prevent postoperative delirium in elderly patients: a randomized, open-label prospective trial. Surg Today. 2014 Dec;44(12):2305-13. doi: 10.1007/s00595-014-0859-7. Epub 2014 Feb 16. — View Citation

Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007 May;55(5):780-91. Review. — View Citation

Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008 Jan 14;168(1):27-32. doi: 10.1001/archinternmed.2007.4. — View Citation

Salluh JI, Wang H, Schneider EB, Nagaraja N, Yenokyan G, Damluji A, Serafim RB, Stevens RD. Outcome of delirium in critically ill patients: systematic review and meta-analysis. BMJ. 2015 Jun 3;350:h2538. doi: 10.1136/bmj.h2538. Review. — View Citation

Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, Chen KS, Gu XE, Zhu SN. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial*. Crit Care Med. 2012 Mar;40(3):731-9. doi: 10.1097/CCM.0b013e3182376e4f. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurence of delirium	Will prophylactic haloperidol in high risk patients as established with DEMO reduce the incidence of delirium?	Delirium within 5 days postoperative
Secondary	Costs of treatment	Total costs of hospital stay	up to 2 years
Secondary	Days admitted to hospital	Total amount of days admitted to the hospital	an average of two weeks
Secondary	Adverse events of intervention medication	Adverse events during admission in the hospital	an average of two weeks
Secondary	Circulating concentration of Haloperidol	Blood sample collection at day, trough concentration haloperidol in blood sample	up to 2 years
Secondary	Duration of delirium	Days DOS (Delirium observation scale) positive after surgery,	an average of two weeks
Secondary	Severity of delirium	DOS scores during admission	an average of two weeks