Efficacy of Atorvastatin in Chronic Subdural Haematoma (REACH)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Subdural Hematoma
• Intervention / Treatment: Drug: Atorvastatin 20mg; Drug: Placebos

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.

• Study Type: Interventional
• Enrollment (Anticipated): 690
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wai Sang Poon, MBChB-Glasg FRCSEd FHKAM-Surg; Phone Number: +852 3505 2624 / 3505 1522; Email: poonws@surgery.cuhk.edu.hk

Study Locations

• Hong Kong
  • Chai Wan, Hong Kong
    • Recruiting
    • Pamela Youde Nethersole Eastern Hospital
    • Contact: Shing Kit Chan, MBBS, MRCS(Ed), MHKICBSC
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital
    • Contact: (Site PI) Anderson Chun On Tsang, MBBS(Hons),MHKICBSC,MRCS(Ed)
  • Kowloon, Hong Kong
    • Recruiting
    • Queen Elizabeth Hospital
    • Contact: (Site PI) Calvin Hoi Kwan Mak, MBBS,MRCS,FRCSEd(SN),FHKAM
  • Kowloon, Hong Kong
    • Recruiting
    • Princess Margaret Hospital
    • Contact: (Site PI) Kwan Ho Chow, MBChB,HKICBS,FCSHK
  • Kowloon, Hong Kong
    • Recruiting
    • Kwong Wah Hospital
    • Contact: (Site PI) Peter Yat Ming Woo, MBBS,MMedSc,FRCS,FCSHK,FHKAM
  • Tuen Mun, Hong Kong
    • Recruiting
    • Tuen Mun Hospital
    • Contact: (Site PI) Jason Man Kit Ho, MBChB (CUHK)
  • New Territories
    • Shatin, New Territories, Hong Kong
      • Recruiting
      • Prince of Wales Hospital
      • Contact: Wai Sang Poon, MBChB-Glasg FRCSEd FHKAM-Surg; Phone Number: +852 3505 2624 / 3505 1522; Email: poonws@surgery.cuhk.edu.hk
      • Principal Investigator: Wai Sang Poon, MBChB-Glasg FRCSEd FHKAM-Surg
      • Sub-Investigator: David Yuen Chung Chan, MRCSEd
      • Sub-Investigator: George Kwok Chu Wong, MBChB,MD,FRCSEd,FCSHK-Surg
      • Sub-Investigator: Stephanie Chi Ping Ng, PhD
      • Sub-Investigator: William B Goggins, ScD, SM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glasgow Outcome Scale (GOS)	Gross clinical outcome measure which allows standardised descriptions (good recovery, moderate disability, severe disability, persistent vegetative state, and death, with good recovery indicating the best outcome and death indicating the worst) for the degree of recovery in patients with brain damage.	2 weeks, 8 weeks, 3 months, and 6 months
Imaging diagnosis	Computed Tomography (CT) brain scan to exclude the presence of air and new blood in subdural space at 1-2 weeks and to elevate the clarification of CSDH resolution at 3 months and 6 months.	Index admission, 1-2 weeks early post-operation or before discharge, 3 months, 6 months
Barthel Index (BI)	Ordinal scale used to measure performance in activities of daily living (ADL) which uses 10 variables describing ADL and mobility. Scores range from 0-100 with 0 indicating the worst outcome and 100 indicating the best outcome.	2 weeks, 8 weeks, 3 months, and 6 months
Montreal Cognitive Assessment (MoCA)	One-page test for detecting cognitive impairment. The score ranges from 0-30 with a higher score indicating better outcome.	2 weeks, 8 weeks, 3 months, and 6 months
Modified Rankin Scale	Scale for measuring the degree of disability or dependence in the daily activities of patients with brain injury.	2 weeks, 8 weeks, 3 months, and 6 months

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Wai Sang Poon, MBChB-Glasg FRCSEd FHKAM-Surg, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2020
• Primary Completion (Anticipated): September 16, 2022
• Study Completion (Anticipated): March 16, 2023

Study Registration Dates

• First Submitted: May 10, 2019
• First Submitted That Met QC Criteria: May 17, 2019
• First Posted (Actual): May 20, 2019

Study Record Updates

• Last Update Posted (Actual): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 19, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Atorvastatin; Clinical outcome; Surgical recurrence; Medical treatment; Chronic subdural haematoma
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Hematoma; Hematoma, Subdural; Hematoma, Subdural, Chronic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: REACH-v1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No