Yiqi Huayu Jiedu Therapy for Non-Surgical Supratentorial Hypertensive Intracerebral Hemorrhage

Official title

Clinical Study of Yiqi Huayu Jiedu Therapy in Non-Surgical Patients With Supratentorial Hypertensive Intracerebral Hemorrhage

Overview

This multicenter, prospective, double-blind, randomized controlled trial will enroll 902 non-surgical patients with supratentorial hypertensive intracerebral hemorrhage who meet the traditional Chinese medicine syndrome criteria of Qi deficiency with blood stasis and toxin-induced injury to the brain collaterals. The primary efficacy endpoint is the proportion of patients achieving a favorable outcome, defined as a modified Rankin Scale score of 0-2 at 180 days after treatment. Participants will be allocated across three trial regions: South China, Northeast China, and East China, with target enrollments of 400, 300, and 202 patients, respectively. Using a central randomization system, patients will be stratified by study center, hematoma volume, and severity of neurological deficit, and randomized 1:1 to the experimental group or control group. The experimental group will receive Yiqi Huayu Jiedu Mixture, composed of red ginseng, Panax notoginseng, and raw rhubarb, while the control group will receive a matching placebo. Both interventions will be administered for 28 days, in addition to standardized conventional Western medical treatment. Clinical and imaging data will be collected at multiple time points throughout the study. The primary outcome is the favorable prognosis rate at 180 days. Secondary outcomes include neurological function, quality of life, hematoma and perihematomal edema volume, and other relevant indicators. Adverse events will be monitored to evaluate the safety and efficacy of the mixture in reducing mortality and disability among patients with hypertensive intracerebral hemorrhage.

Interventions

• Drug Yiqi Huayu Jiedu Mixture Intervention
  Yiqi Huayu Jiedu Mixture, composed of red ginseng, Panax notoginseng, and raw rhubarb
• Drug The placebo
  The placebo is matched to the Yiqi Huayu Jiedu mixture in terms of outer packaging, appearance, odor, taste, and other identifiable characteristics to ensure blinding.

Primary outcome measures

• the favorable prognosis rate [Time frame: at 180 days]

Secondary outcome measures (5)

• Ordinal mRS outcome data [Time frame: at 28, 90, and 180 days]
• NIHSS scores [Time frame: at 7, 14, and 28 days]
• EQ-5D-5L scores [Time frame: at 28, 90, and 180 days]
• Hematoma volume and perihematomal edema volume [Time frame: at 7 days, 14 days, or discharge.]
• GCS score [Time frame: at days 7, 14, and 28]

Eligibility criteria

Inclusion criteria

1.Adults aged 18 years or older, with no restriction on sex. 2.6 to 48 hours after symptom onset; if the exact onset time cannot be determined, the time shall be calculated from the last known well.

3.Patients meeting the traditional Chinese medicine syndrome criteria of "Qi deficiency, blood stasis, and toxin-induced injury to the brain collaterals." Diagnosis shall be based on the Expert Consensus on Integrated Traditional Chinese and Western Medicine for Cerebral Hemorrhage (T/CAIM 023-2021) issued by the Chinese Association of Integrative Medicine.

4.Imaging-confirmed supratentorial hypertensive intracerebral hemorrhage (HICH) located in the basal ganglia, thalamus, lobar region, or subcortical white matter, with a hematoma volume of 15-60 mL.

5.NIHSS score ≥ 8 and GCS score > 7. 6.The patient or the patient's legally authorized representative has provided written informed consent

Exclusion criteria

Patients meeting \*\*one or more\*\* of the following criteria will be excluded:

• Intracerebral hemorrhage secondary to structural brain abnormalities, including but not limited to cerebral vascular malformation, intracranial aneurysm, malignant tumor, moyamoya disease, trauma, previous ischemic stroke, cerebral amyloid angiopathy, thrombolysis or thrombectomy, anticoagulant therapy, or other causes of secondary intracerebral hemorrhage.
• Patients who, in the judgment of the treating physician, are unlikely to benefit from the trial, have an extremely high risk of early death, or are considered unsuitable for participation by the investigator, such as patients with advanced dementia.
• Conditions that may interfere with follow-up or outcome assessment, such as known significant pre-stroke disability, modified Rankin Scale score of 3-5, end-stage malignancy, or renal failure.
• Indications for decompressive craniectomy, including but not limited to coma or progressive deterioration of consciousness, large hematoma with significant midline shift, intracranial hypertension difficult to control with medical treatment, cerebral herniation or impending herniation, or marked mass effect on imaging, such as midline shift >10 mm or compression/disappearance of cisterns or sulci.
• Known allergy to any traditional Chinese medicine component of the mixture.
• Pregnant or lactating women.
• Participation in another clinical trial that may interfere with the evaluation of this 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

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Wu B, Liu M, Liu H, Li W, Tan S, Zhang S, Fang Y. Meta-analysis of traditional Chinese patent medicine for ischemic stroke. Stroke. 2007 Jun;38(6):1973-9. doi: 10.1161/STROKEAHA.106.473165. Epub 2007 Apr 26. PMID 17463317
• Wan Y, Holste KG, Hua Y, Keep RF, Xi G. Brain edema formation and therapy after intracerebral hemorrhage. Neurobiol Dis. 2023 Jan;176:105948. doi: 10.1016/j.nbd.2022.105948. Epub 2022 Dec 5. PMID 36481437
• Ma L, Hu X, Song L, Chen X, Ouyang M, Billot L, Li Q, Malavera A, Li X, Munoz-Venturelli P, de Silva A, Thang NH, Wahab KW, Pandian JD, Wasay M, Pontes-Neto OM, Abanto C, Arauz A, Shi H, Tang G, Zhu S, She X, Liu L, Sakamoto Y, You S, Han Q, Crutzen B, Cheung E, Li Y, Wang X, Chen C, Liu F, Zhao Y, Li H, Liu Y, Jiang Y, Chen L, Wu B, Liu M, Xu J, You C, Anderson CS; INTERACT3 Investigators. The th PMID 37245517
• Zhai Z, Su PW, Ma LY, Yang H, Wang T, Fei ZG, Zhang YN, Wang Y, Ma K, Han BB, Wu ZC, Yu HY, Zhao HJ. Progress on traditional Chinese medicine in treatment of ischemic stroke via the gut-brain axis. Biomed Pharmacother. 2023 Jan;157:114056. doi: 10.1016/j.biopha.2022.114056. Epub 2022 Nov 26. PMID 36446240
• Pradilla G, Ratcliff JJ, Hall AJ, Saville BR, Allen JW, Paulon G, McGlothlin A, Lewis RJ, Fitzgerald M, Caveney AF, Li XT, Bain M, Gomes J, Jankowitz B, Zenonos G, Molyneaux BJ, Davies J, Siddiqui A, Chicoine MR, Keyrouz SG, Grossberg JA, Shah MV, Singh R, Bohnstedt BN, Frankel M, Wright DW, Barrow DL; ENRICH trial investigators; ENRICH Trial Investigators. Trial of Early Minimally Invasive Remova PMID 38598795
• GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021 Oct;20(10):795-820. doi: 10.1016/S1474-4422(21)00252-0. Epub 2021 Sep 3. PMID 34487721
• Seiffge DJ, Anderson CS. Treatment for intracerebral hemorrhage: Dawn of a new era. Int J Stroke. 2024 Jun;19(5):482-489. doi: 10.1177/17474930241250259. PMID 38803115

Identifiers

NCT: NCT07580235 · BF2026-084-01 · 2026ZD0555303

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗