## Protocol Section
### Identification Module
**NCT ID:** NCT06427980

**Acronym:** CHARM

**Brief Title:** Efficacy and Safety of Chinese Herbal Formula HuoXue LiShui for Chronic Subdural Hematoma

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

#### Organization Study ID Info
**ID:** KY2023-265
#### Organization
**Class:** OTHER
**Full Name:** Beijing Tiantan Hospital
### Status Module
#### Completion Date
**Date:** 2025-02-28

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-02-28

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-20
**Study First Submit QC Date:** 2024-05-23
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Beijing Tiantan Hospital

#### Responsible Party

**Investigator Affiliation:** Beijing Tiantan Hospital

**Investigator Full Name:** Weiming Liu

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** A prospective, randomized, double-blinded, placebo-controlled, multicenter trail is designed to compare differences of operation rate and clinical outcome from treatment up to 24 weeks between HXLS group and placebo group.

**Detailed Description:** The CHARM trial is a prospective, randomized, double-blinded, placebo-controlled, multicenter clinical study. The trial aims to investigate the efficacy of Chinese herbal formula HXLS as an addition to a primary conservative treatment of CSDH, in an effort to prevent surgery. We hypothesize that compared with placebo, Chinese herbal formula HXLS reduces operation rates 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 placebo group at 1:1 ratio.

### Conditions Module

**Conditions:**

- Chronic Subdural Hematoma

**Keywords:**

- Chronic Subdural Hematoma

- Chinese herbal formula

- HuoXue LiShui

- Pharmacotherapy

- Randomized controlled trial

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** The investigators in charge of the recruitment and follow-up evaluation and participants will be blinded, along with the outcome assessors and data analysts.

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 160

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** The HXLS granules are produced from four Chinese herbal pieces: Yi Mu Cao (益母草, Leonurus heterophyllus, 15.0g), Zhi Shui Zhi (炙水蛭, Hirudo, 1.5g), Tao Ren (桃仁, Semen persicae, 6.0g), and Hong Hua (红花, Carthamus tinctorius L, 6.0g).

**Intervention Names:**

- Drug: Chinese Herbal formula HuoXue LiShui

**Label:** HXLS group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** The placebo will be consistent with the HXLS oral granules in appearance, taste, and weight, to the greatest extent possible. It included Hu Jing (糊精 28.0g)

**Intervention Names:**

- Drug: Chinese Herbal formula Placebo

**Label:** placebo group

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- HXLS group

**Description:** 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 (益母草, Leonurus heterophyllus, 15.0g), Zhi Shui Zhi (炙水蛭, Hirudo, 1.5g), Tao Ren (桃仁, Semen persicae, 6.0g), and Hong Hua (红花, Carthamus tinctorius L, 6.0g).

**Name:** Chinese Herbal formula HuoXue LiShui

**Other Names:**

- HuoXue LiShui

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- placebo group

**Description:** 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)

**Name:** Chinese Herbal formula Placebo

**Other Names:**

- Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Rate of operation

**Measure:** Rate of operation

**Time Frame:** From baseline up to 24 weeks after the start of treatment with the study medication

#### Secondary Outcomes

**Description:** CSDH volume measured on head CT

**Measure:** Chronic subdural hematoma volume

**Time Frame:** At baseline, and at 4, 12, and 24 weeks

**Description:** 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.

**Measure:** Change of Modified Rankin Scale (MRS) between group

**Time Frame:** At baseline, and at 1, 4, 8, 12, and 24 weeks

**Description:** 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.

**Measure:** Change of Markwalder Grading Scale (MGS) between groups

**Time Frame:** At baseline, and at 1, 4, 8, 12, and 24 weeks

**Description:** 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'.

**Measure:** Change of Quality of life

**Time Frame:** At baseline, and at 4, 8, 12, and 24 weeks

**Description:** 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.

**Measure:** Change of performance in activities of daily living

**Time Frame:** At baseline, and at 4, 8, 12, and 24 weeks

**Description:** Montreal Cognitive Assessment, MOCA score

**Measure:** Change of cognitive functioning

**Time Frame:** At baseline, and at 4, 8, 12, and 24 weeks

**Description:** Number of falling incidents

**Measure:** Number of falling incidents

**Time Frame:** At 24 weeks

**Description:** Mortality

**Measure:** Mortality

**Time Frame:** At 24 weeks

**Description:** Rate of complications and adverse events between groups

**Measure:** Rate of complications and adverse events between groups

**Time Frame:** Within 24 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Age between 18 years and 90 years and either gender.
2. Supratentorial, unilateral or bilateral CSDH verified on cranial CT or magnetic resonance imaging.
3. Stable vital signs and neurological deficit with GCS score ≥ 14 and modified Rankin Scale (mRS) score ≤ 2.
4. No risk of brain herniation and recent immediate needs for surgery evaluated by 2 attending neurosurgeons.
5. Written informed consent from patients or their next of kin according to the patient's 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 GCS score \< 14 or mRS score \> 2.
3. Midline shift \> 10 mm on radiological image.
4. Previous treatment (surgery or medication) for CSDH.
5. Previous intracranial surgery for any other neurological disorders.
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 tumor.
9. Abnormal liver function or liver diseases including uncontrolled hepatitis (alanine transaminase \> 120U/L).
10. Severe renal impairment (estimated glomerular filtration rate \< 30ml/min or serum creatinine \> 150μmol/L).
11. Moderate or severe anemia (hemoglobin ≤ 90g/L).
12. Severe coagulopathy or high risk of life-threatening bleeding.
13. Existing poor medication condition or severe comorbidity so that treatment cannot be tolerated, or follow-up cannot be completed.
14. Routine oral antithrombotic or antifibrinolytic drugs, steroids, statins, or other traditional Chinese medicine before randomization or who are expected to take such medications in the next 24 weeks.
15. Difficulty in swallowing oral medication.
16. Pregnancy or lactation.
17. Participating in another research.

**Maximum Age:** 90 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** wuliang@bjtth.org

**Name:** Liang Wu, M.D.

**Phone:** 15001333582

**Role:** CONTACT

**Contact 2:**

**Email:** liuweimingnsok@sina.com

**Name:** Weiming Liu, M.D.

**Phone:** 13701182770

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Country:** China

**Facility:** Beijing Luhe Hospital, Capital Medical University

**State:** Beijing

**Zip:** 101100

**Location 2:**

**City:** Lianyungang

**Country:** China

**Facility:** First People's Hospital of Lianyungang

**State:** Jiangsu

**Location 3:**

**City:** Beijing

**Country:** China

**Facility:** Beijing Tiantan Hospital, Capital Medical University

**Zip:** 100070

#### Overall Officials

**Official 1:**

**Affiliation:** Beijing Tiantan Hospital

**Name:** Weiming Liu, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006470

- Term: Hemorrhage

- ID: D000010335

- Term: Pathologic Processes

- ID: D000020198

- Term: Intracranial Hemorrhage, Traumatic

- ID: D000020300

- Term: Intracranial Hemorrhages

- ID: D000002561

- Term: Cerebrovascular Disorders

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000006259

- Term: Craniocerebral Trauma

- ID: D000020196

- Term: Trauma, Nervous System

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000014947

- Term: Wounds and Injuries

- ID: D000002908

- Term: Chronic Disease

- ID: D000020969

- Term: Disease Attributes

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC26

- Name: Wounds and Injuries

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M9493

- Name: Hematoma

- Relevance: HIGH

- As Found: Hematoma

- ID: M9495

- Name: Hematoma, Subdural

- Relevance: HIGH

- As Found: Subdural Hematoma

- ID: M22027

- Name: Hematoma, Subdural, Chronic

- Relevance: HIGH

- As Found: Chronic Subdural Hematoma

- ID: M9556

- Name: Hemorrhage

- Relevance: LOW

- As Found: Unknown

- ID: M22113

- Name: Intracranial Hemorrhages

- Relevance: LOW

- As Found: Unknown

- ID: M22025

- Name: Intracranial Hemorrhage, Traumatic

- Relevance: LOW

- As Found: Unknown

- ID: M5810

- Name: Cerebrovascular Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17685

- Name: Wounds and Injuries

- Relevance: LOW

- As Found: Unknown

- ID: M9349

- Name: Craniocerebral Trauma

- Relevance: LOW

- As Found: Unknown

- ID: M22023

- Name: Trauma, Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: HIGH

- As Found: Chronic

### Condition Browse Module - Meshes

- ID: D000006408

- Term: Hematoma, Subdural

- ID: D000020200

- Term: Hematoma, Subdural, Chronic

- ID: D000006406

- Term: Hematoma

### Misc Info Module

- Version Holder: 2024-05-31
