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

Official title

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

Overview

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.

Interventions

• 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).
• 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)

Primary outcome measures

• Rate of operation [Time frame: From baseline up to 24 weeks after the start of treatment with the study medication]

Secondary outcome measures (9)

• Chronic subdural hematoma volume [Time frame: At baseline, and at 4, 8 and 24 weeks]
• Change of Modified Rankin Scale (MRS) between group [Time frame: At baseline, and at 4, 8, and 24 weeks]
• Change of Markwalder Grading Scale (MGS) between groups [Time frame: At baseline, and at 4, 8, and 24 weeks]
• Change of Quality of life [Time frame: At baseline, and at 4, 8, and 24 weeks]
• Change of performance in activities of daily living [Time frame: At baseline, and at 4, 8, and 24 weeks]
• Change of cognitive functioning [Time frame: At baseline, and at 4, 8, and 24 weeks]
• Number of falling incidents [Time frame: At 24 weeks]
• Mortality [Time frame: At 24 weeks]
• Rate of complications and adverse events between groups [Time frame: Within 24 weeks]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Unstable vital signs or symptoms of brain herniation, including severe headache, nausea and vomiting, or disturbed consciousness.
• Progressive or apparent neurological deficit with a GCS score < 14 or mRS score > 2.
• Midline shift > 10 mm on the radiological image.
• Previous medication treatment for CSDH.
• Previous intracranial surgery for any other neurological disorder.
• Structural causes for secondary CSDH, including arachnoid cysts, intracranial tumors, vascular malformations, spontaneous intracranial hypotension, coagulopathy, and conversion from acute subdural hematoma.
• Known hypersensitivity or allergy to HXLS or to any of the ingredients.
• Malignant tumors.
• Life expectancy of < 1 year.
• Abnormal liver function or liver diseases, including uncontrolled hepatitis (alanine transaminase > 120 U/L).
• Severe renal impairment (estimated glomerular filtration rate < 30 ml/min or serum creatinine > 150 μmol/L).
• Moderate or severe anemia (hemoglobin ≤ 90 g/L).
• Severe coagulopathy or a high risk of life-threatening bleeding.
• Poor medication conditions or the presence of severe comorbidities such that treatment cannot be tolerated or follow-up cannot be completed.
• 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.
• Difficulty swallowing oral medication.
• Pregnancy or lactation.
• Participating in another study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 3 centers

• Beijing Luhe Hospital, Capital Medical University — Beijing
• First People's Hospital of Lianyungang — Lianyungang
• Beijing Tiantan Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT06427980 · KY2023-265

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗