Efficacy of Atorvastatin in Chronic Subdural Haematoma

Study Overview
=================
Brief Summary
-----------------
This prospective, double-blind, randomized, placebo-controlled study aims to evaluate the efficacy and safety of atorvastatin in patients with chronic subdural haematoma. The degree of disability or dependence in daily activities, as well as surgical intervention or recurrence, of the treatment and control groups will be compared.

Detailed Description
-----------------
Objectives: Chronic subdural haematoma (CSDH) is a common neurosurgical condition in the elderly population associated with mild head injury. Surgical drainage has been regarded as safe and effective. However, surgical complications including recurrences can result in poor functional outcome and fatality, particularly in the elderly patients. Atorvastatin, an HMGCoA reductase inhibitor and a widely prescribed lipid lowering medication has properties of inflammation modulation and neovasculature promotion. Hypothesis: Atorvastatin can improve functional outcome in patients with CSDH for both initially non-operatively treated group (estimated to be 10%) and the operative group (90%) by reducing the rate of surgical intervention and recurrence rate. Design: A prospective multicentre study of 690 consented patients with symptomatic CSDH will be randomised on the day of admission to receive atorvastatin 20 mg or a placebo daily for 8 weeks. All seven regional neurosurgical units in Hong Kong and two units outside Hong Kong, each treating 80-200 patients per annum, have been invited to participate. Main Outcome Measures: Primary outcome: Modified Rankin Scale (mRS). Secondary outcome: surgical recurrence. Sample Size: Assuming an absolute 10% improvement in favourable outcome in the Modified Rankin Scale score (mRS 0-3) at 6 months from the control group of 70% to the treatment group 80%, allowing a 10% loss to follow up, a sample size of 690 is required. Expected Results: A successful study for improving clinical outcome of CSDH, an important illness of the elderly with an annual incidence of 58/100,000 will change clinical practice.

Official Title
-----------------
A Randomised, Double-blind, Placebo-controlled Trial on the Efficacy of Atorvastatin in Chronic Subdural Haematoma (The REACH Study)

Conditions
-----------------
Chronic Subdural Hematoma

Intervention / Treatment
-----------------
* Drug: Atorvastatin 20mg
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age greater than or equal to 18 years old; Evidence of supratentorial chronic subdural haematoma (unilateral or bilateral) by Computed Tomography (CT); Patients are joining the trial voluntarily with consent form signed. Exclusion Criteria: Allergy to atorvastatin or other statins; Deranged liver function; Patients who are already on long term steroid for other condition(s); Patients who are already on statin for other condition(s); Presence of cerebrospinal fluid diversion device (e.g. ventriculo-peritoneal shunt); Pregnant or on breast feeding; Hematoma is secondary to tumour or haematological disorders; Patients taking angiotensin converting enzyme (ACE) inhibitor.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible subjects will be randomised upon admission to receive atorvastin 20mg nocte or placebo for 8 weeks.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Randomised on the day of admission to receive oral Atorvastatin 20mg daily for 8 weeks. | Drug: Atorvastatin 20mg<br>* 20mg (every evening orally) for 8 weeks.<br>|
| Placebo Comparator: Control Group<br>Randomised on the day of admission to receive placebo 20mg daily for 8 weeks. | Drug: Placebos<br>* 20mg (every evening orally) for 8 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Favourable Modified Rankin Scale (mRS) score | Modified Rankin Scale score of 0-3 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic subdural haematoma (CSDH) related surgical intervention | Recurrence rate in both initially non-operatively treated patients and operative cases | Throughout the study period, an average of 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Medical treatment, Chronic subdural haematoma, Atorvastatin, Clinical outcome, Surgical recurrence