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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Delirium

Intervention / Treatment
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* Drug: Haloperidol
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prophylactic Haloperidol arm<br>Patients will receive oral haloperidol 2dd1mg (08.00am & 10.00pm) | Drug: Haloperidol<br>* Haloperidol 2dd1mg (08.00am - 10.00pm)<br>* Other names: RVG 55776;|
| Placebo Comparator: No treatment<br>Patients will receive oral placebo 2dd (08.00am & 10.00pm) | Drug: Placebo Oral Tablet<br>* Placebo oral 2dd (08.00am - 10.00pm)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Costs of treatment | Total costs of hospital stay | up to 2 years | 
| Days admitted to hospital | Total amount of days admitted to the hospital | an average of two weeks | 
| Adverse events of intervention medication | Adverse events during admission in the hospital | an average of two weeks | 
| Circulating concentration of Haloperidol | Blood sample collection at day, trough concentration haloperidol in blood sample | up to 2 years | 
| Duration of delirium | Days DOS (Delirium observation scale) positive after surgery, | an average of two weeks | 
| Severity of delirium | DOS scores during admission | an average of two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Delirium, Haloperidol, Prophylactic, High-risk