A prospective, randomised, double-blind, placebo-controlled, multicentre trial was designed to compare the the incidence of hematoma progression requiring operation or hematoma recurrence requiring re-operation and improves clinical outcomes at 24 weeks in patients with CSDH of treatment in the HXLS and placebo groups.
The CHARM trial is a prospective, randomized, double-blinded, placebo-controlled, multicenter clinical study. The trial aims to investigate the efficacy of the Chinese herbal formula HXLS as an addition to a primary conservative treatment of CSDH in an effort to prevent surgery. The investigators hypothesize that, compared with placebo, the Chinese herbal formula HXLS reduce incidence of hematoma progression requiring operation or hematoma recurrence requiring re-operation and improves clinical outcomes at 24 weeks in patients with CSDH. Consequently, the defined null hypothesis will be that there is no difference between the groups. In total, 160 patients will be randomly assigned to the HXLS group and the placebo group at a 1:1 ratio.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
160
The intervention consists of the oral administration of granule with either HXLS or a placebo substance, one bag (28.5 g) twice daily after meals for a period of 8 weeks. The granules are produced from four Chinese herbal pieces: Yi Mu Cao (Leonuri Herbal, 15.0g), Zhi Shui Zhi (Hirudo, 1.5g), Tao Ren (Semen persicae, 6.0g), and Hong Hua (Carthami Flos, 6.0g).
The placebo will be consistent with the HXLS oral granules in appearance, taste, and weight, to the greatest extent possible. In terms of outer packing, the HXLS and placebo granules will be exactly the same. It included Hu Jing (28.5g)
Beijing Luhe Hospital, Capital Medical University
Beijing, Beijing Municipality, China
First People's Hospital of Lianyungang
Lianyungang, Jiangsu, China
Beijing Tiantan Hospital, Capital Medical University
Beijing, China
Rate of operation
Surgical rate of hematoma recurrence due to progression of primary hematoma or after burr hole drainage
Time frame: From baseline up to 24 weeks after the start of treatment with the study medication
Chronic subdural hematoma volume
CSDH volume measured on head CT
Time frame: At baseline, and at 4, 8 and 24 weeks
Change of Modified Rankin Scale (MRS) between group
Modified Rankin Scale ranges from score 1 to 6, and higher scores mean a worse clinical outcome, where score 1 indicates normal daily functionality and score 6 indicates death.
Time frame: At baseline, and at 4, 8, and 24 weeks
Change of Markwalder Grading Scale (MGS) between groups
Markwalder Grading Scale ranges from grade 0 to 4, and higher scores mean a worse neurological outcome, where grade 0 indicates normal neurological function and grade 4 indicates coma.
Time frame: At baseline, and at 4, 8, and 24 weeks
Change of Quality of life
A standardized instrument, EuroQoL 5-Dimension 5-Level (EQ-5D-5L) questionnaire, will be used as a generic measure of health related quality of life. The questionnaire contains 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension rates across five levels, including 'No problems-Slight problems-Moderate problems-Severe problems-Unable to'.
Time frame: At baseline, and at 4, 8, and 24 weeks
Change of performance in activities of daily living
The Barthel Index is scored from 0 to 100. \>60 is good, with mild dysfunction, able to perform some activities of daily living independently, and needing some help; 60-41 is moderate. 60-41 is classified as moderate, with moderate dysfunction, requiring a great deal of help to complete activities of daily living; ≤40 is classified as poor, with severe dysfunction, unable to complete most of the activities of daily living or needing help from others.
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Time frame: At baseline, and at 4, 8, and 24 weeks
Change of cognitive functioning
The Montreal Cognitive Assessment (MOCA) score is an assessment tool designed to facilitate rapid screening for abnormalities in cognitive functioning. It encompasses 11 screening items across eight cognitive domains, including attention and concentration, executive function, memory, language, visual structural skills, abstract thinking, calculation, and orientation. A total score of 30 or above 26 is indicative of normal cognitive function.
Time frame: At baseline, and at 4, 8, and 24 weeks
Number of falling incidents
Number of falling incidents
Time frame: At 24 weeks
Mortality
Mortality
Time frame: At 24 weeks
Rate of complications and adverse events between groups
Rate of complications and adverse events between groups
Time frame: Within 24 weeks