Clinical trial NCT03199950: PROfylactic Haloperidol in Patients Defined as High Risk for DElirium With Delirium Risk mOdel
Official title: Delirium: Is Prophylactic Drug Therapy Useful in High Risk Patients as Defined by the Delirium Risk Prediction Model?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Delirium
Keywords: Delirium
Haloperidol
Prophylactic
High-risk
Lead sponsor: Zuyderland Medisch Centrum
Sponsor class: OTHER
First posted: 2017-06-27
Enrollment: 1366
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurence of delirium
timeFrame: Delirium within 5 days postoperative
Secondary outcomes:
measure: Costs of treatment
timeFrame: up to 2 years
measure: Days admitted to hospital
timeFrame: an average of two weeks
measure: Adverse events of intervention medication
timeFrame: an average of two weeks
measure: Circulating concentration of Haloperidol
timeFrame: up to 2 years
measure: Duration of delirium
timeFrame: an average of two weeks
measure: Severity of delirium
timeFrame: an average of two weeks
Other outcomes:
Locations:
city: Sittard
country: Netherlands
facility: Zuyderland Medisch Centrum
state: Limburg
Study officials:
affiliation: Zuyderland MC
name: Hugo van der Kuy
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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.
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.
citation: 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.