Efficacy and Safety of Chinese Herbal HuoXue LiShui Formula for Chronic Subdural Hematoma

Not Applicable

Not yet recruiting

• Conditions: Chronic Subdural Hematoma
• Interventions: Drug: Chinese Herbal formula Placebo; Drug: Chinese Herbal formula HuoXue LiShui

• Registration Number: NCT06427980
• Lead Sponsor: Beijing Tiantan Hospital

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2024-05-20
• Study First Submitted QC: 2024-05-23
• Study First Posted: 2024-05-24
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-26
• Last Update Posted: 2024-12-30
• Study Start: 2025-02-01
• Primary Completion: 2025-12-01
• Study Completion: 2026-03-28

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1. Age between 18 and 90 years and either gender will be included.
2. Supratentorial, unilateral or bilateral CSDHs will be verified via cranial CT or magnetic resonance imaging (MRI).
3. Primary hematoma or residual hematoma after burr-hole drainage.
4. Stable vital signs and neurological deficits are indicated by a Glassgow Coma Scale (GCS) score ≥ 14 and a modified Rankin scale (mRS) score ≤ 2.
5. No risk of brain herniation or recent immediate need for surgery will be evaluated by 2 attending neurosurgeons.
6. Written informed consent will be obtained from patients or their next of kins according to their cognitive status.

Exclusion Criteria

1. Unstable vital signs or symptoms of brain herniation, including severe headache, nausea and vomiting, or disturbed consciousness.
2. Progressive or apparent neurological deficit with a GCS score < 14 or mRS score > 2.
3. Midline shift > 10 mm on the radiological image.
4. Previous medication treatment for CSDH.
5. Previous intracranial surgery for any other neurological disorder.
6. Structural causes for secondary CSDH, including arachnoid cysts, intracranial tumors, vascular malformations, spontaneous intracranial hypotension, coagulopathy, and conversion from acute subdural hematoma.
7. Known hypersensitivity or allergy to HXLS or to any of the ingredients.
8. Malignant tumors.
9. Life expectancy of < 1 year.
10. Abnormal liver function or liver diseases, including uncontrolled hepatitis (alanine transaminase > 120 U/L).
11. Severe renal impairment (estimated glomerular filtration rate < 30 ml/min or serum creatinine > 150 μmol/L).
12. Moderate or severe anemia (hemoglobin ≤ 90 g/L).
13. Severe coagulopathy or a high risk of life-threatening bleeding.
14. Poor medication conditions or the presence of severe comorbidities such that treatment cannot be tolerated or follow-up cannot be completed.
15. Routine oral antithrombotic or antifibrinolytic drugs, steroids, statins, angiotensin-converting enzyme inhibitors, or other traditional Chinese medicines before randomization or are expected to take such medications in the next 24 weeks.
16. Difficulty swallowing oral medication.
17. Pregnancy or lactation.
18. Participating in another study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo group	Chinese Herbal formula Placebo	The placebo will be consistent with the HXLS oral granules in appearance, taste, and weight, to the greatest extent possible. It included Hu Jing (28.0g)
HXLS group	Chinese Herbal formula HuoXue LiShui	The HXLS granules are produced from four Chinese herbal pieces: Yi Mu Cao (Leonurus heterophyllus, 15.0g), Zhi Shui Zhi (Hirudo, 1.5g), Tao Ren (Semen persicae, 6.0g), and Hong Hua (Carthamus tinctorius L, 6.0g).

Primary Outcome Measures

Name	Time	Method
Rate of operation	From baseline up to 24 weeks after the start of treatment with the study medication	Surgical rate of hematoma recurrence due to progression of primary hematoma or after burr hole drainage

Secondary Outcome Measures

Name	Time	Method
Chronic subdural hematoma volume	At baseline, and at 4, 8 and 24 weeks	CSDH volume measured on head CT
Number of falling incidents	At 24 weeks	Number of falling incidents
Change of Modified Rankin Scale (MRS) between group	At baseline, and at 4, 8, and 24 weeks	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.
Change of performance in activities of daily living	At baseline, and at 4, 8, and 24 weeks	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.
Rate of complications and adverse events between groups	Within 24 weeks	Rate of complications and adverse events between groups
Change of Markwalder Grading Scale (MGS) between groups	At baseline, and at 4, 8, and 24 weeks	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.
Change of Quality of life	At baseline, and at 4, 8, and 24 weeks	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'.
Change of cognitive functioning	At baseline, and at 4, 8, and 24 weeks	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.
Mortality	At 24 weeks	Mortality

Trial Locations

Locations (3)

Beijing Luhe Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

First People's Hospital of Lianyungang; 🇨🇳 Lianyungang, Jiangsu, China

Beijing Tiantan Hospital, Capital Medical University; 🇨🇳 Beijing, China