Clinical trial NCT03956368: Efficacy of Atorvastatin in Chronic Subdural Haematoma
Official title: A Randomised, Double-blind, Placebo-controlled Trial on the Efficacy of Atorvastatin in Chronic Subdural Haematoma (The REACH Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Subdural Hematoma
Keywords: Chronic subdural haematoma
Medical treatment
Atorvastatin
Clinical outcome
Surgical recurrence
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2019-05-20
Enrollment: 690
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible subjects will be randomised upon admission to receive atorvastin 20mg nocte or placebo for 8 weeks.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age greater than or equal to 18 years old;
2. Evidence of supratentorial chronic subdural haematoma (unilateral or bilateral) by Computed Tomography (CT);
3. Patients are joining the trial voluntarily with consent form signed.

Exclusion Criteria:

1. Allergy to atorvastatin or other statins;
2. Deranged liver function;
3. Patients who are already on long term steroid for other condition(s);
4. Patients who are already on statin for other condition(s);
5. Presence of cerebrospinal fluid diversion device (e.g. ventriculo-peritoneal shunt);
6. Pregnant or on breast feeding;
7. Hematoma is secondary to tumour or haematological disorders;
8. Patients taking angiotensin converting enzyme (ACE) inhibitor.

Primary outcomes:
measure: Favourable Modified Rankin Scale (mRS) score
timeFrame: 6 months
Secondary outcomes:
measure: Chronic subdural haematoma (CSDH) related surgical intervention
timeFrame: Throughout the study period, an average of 6 months
Other outcomes:
measure: Glasgow Outcome Scale (GOS)
timeFrame: 2 weeks, 8 weeks, 3 months, and 6 months
measure: Imaging diagnosis
timeFrame: Index admission, 1-2 weeks early post-operation or before discharge, 3 months, 6 months
measure: Barthel Index (BI)
timeFrame: 2 weeks, 8 weeks, 3 months, and 6 months
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: 2 weeks, 8 weeks, 3 months, and 6 months
measure: Modified Rankin Scale
timeFrame: 2 weeks, 8 weeks, 3 months, and 6 months
Locations:
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Kowloon
country: Hong Kong
facility: Kwong Wah Hospital
city: Kowloon
country: Hong Kong
facility: Princess Margaret Hospital
city: Kowloon
country: Hong Kong
facility: Queen Elizabeth Hospital
city: Tuen Mun
country: Hong Kong
facility: Tuen Mun Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Wai Sang Poon, MBChB-Glasg FRCSEd FHKAM-Surg
role: PRINCIPAL_INVESTIGATOR
References: