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

Zuyderland Medisch Centrum

Status and phase: Unknown; Phase 4

Conditions: Delirium

Treatments: Drug: Placebo Oral Tablet; Drug: Haloperidol

Study type: Interventional

Funder types: Other

Identifiers

NCT03199950

2017-001260-37 (EudraCT Number)

17-T-31

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,366 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,366 participants in 2 patient groups, including a placebo group

Prophylactic Haloperidol arm

Experimental group

Description:

Patients will receive oral haloperidol 2dd1mg (08.00am \& 10.00pm)

Treatment:

Drug: Haloperidol

No treatment

Placebo Comparator group

Description:

Patients will receive oral placebo 2dd (08.00am \& 10.00pm)

Treatment:

Drug: Placebo Oral Tablet