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

Efficacy and Safety of Chinese Herbal HuoXue LiShui Formula for Chronic Subdural Hematoma: a a Prospective, Randomized, Double-blinded, Placebo-controlled, Multicenter Trail

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Subdural Hematoma
• Intervention / Treatment: Drug: Chinese Herbal formula Placebo; Drug: Chinese Herbal formula HuoXue LiShui

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 Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Weiming Liu, M.D.; Phone Number: 13701182770; Email: liuweimingnsok@sina.com
• Study Contact Backup: Name: Liang Wu, M.D.; Phone Number: 15001333582; Email: wuliang@bjtth.org

Study Locations

• China
  • Beijing, China, 100070
    • Beijing Tiantan Hospital, Capital Medical University
  • Beijing
    • Beijing, Beijing, China, 101100
      • Beijing Luhe Hospital, Capital Medical University
  • Jiangsu
    • Lianyungang, Jiangsu, China
      • First People's Hospital of Lianyungang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 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: HXLS group; 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).	Drug: Chinese Herbal formula HuoXue LiShui; 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).; Other Names: HuoXue LiShui
Placebo Comparator: placebo group; 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)	Drug: Chinese Herbal formula Placebo; 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); Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of falling incidents	Number of falling incidents	At 24 weeks
Mortality	Mortality	At 24 weeks
Rate of complications and adverse events between groups	Rate of complications and adverse events between groups	Within 24 weeks
Chronic subdural hematoma volume	CSDH volume measured on head CT	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.	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.	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'.	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.	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.	At baseline, and at 4, 8, and 24 weeks

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Weiming Liu, M.D., Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 28, 2026

Study Registration Dates

• First Submitted: May 20, 2024
• First Submitted That Met QC Criteria: May 23, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 26, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Chinese herbal formula; Pharmacotherapy; Chronic Subdural Hematoma; HuoXue LiShui
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Chronic Disease; Disease Attributes; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Hematoma, Subdural; Hematoma, Subdural, Chronic; Hematoma
• Other Study ID Numbers: KY2023-265

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No