Hypertension, Intracerebral Hemorrhage
Conditions
Keywords
Huayu Jiedu Formula, Traditional Chinese Medicine, Formula Granules, Non-inferiority Trial
Brief summary
This is a multicenter, randomized, double-blind, controlled, non-inferiority clinical trial to evaluate the efficacy and safety of Huayu Jiedu Formula (FTFY-919) Chinese medicine formula granules compared with traditional decoction in patients with acute hypertensive intracerebral hemorrhage (ICH). A total of 300 eligible patients will be randomized in a 1:1:1 ratio to receive FTFY-919 formula granules, FTFY-919 traditional decoction, or placebo granules for 28 days, in addition to standard western medicine treatment. The primary outcome is the utility-weighted modified Rankin Scale (mRS) score at Day 90. Secondary outcomes include NIHSS score, hematoma volume and perihematomal edema volume, death or severe disability, EQ-5D-5L, Barthel Index and TCM syndrome scores. The trial will be conducted at 5 centers in China.
Detailed description
Hypertensive intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high mortality and disability. Huayu Jiedu Formula (FTFY-919), a traditional Chinese medicine (TCM) formula composed of Radix Ginseng Rubra (30 g), Radix Notoginseng (30 g) and Radix et Rhizoma Rhei (5 g), has long been used in clinical practice for acute ICH. Whether the modern formula granules preparation is non-inferior to the traditional decoction has not been established in a rigorous trial. This is a multicenter, randomized, double-blind, parallel, placebo-controlled, non-inferiority trial. A total of 300 patients with acute hypertensive ICH will be randomly assigned in a 1:1:1 ratio to receive FTFY-919 formula granules, FTFY-919 traditional decoction, or placebo granules for 28 days, all in addition to standard Western medicine treatment. Randomization will be stratified by center and baseline hematoma volume. Granules, decoction-derived granules and placebo have identical appearance and packaging to maintain blinding of participants, care providers, investigators and outcome assessors. The primary outcome is the utility-weighted modified Rankin Scale (uw-mRS) score at Day 90. The primary hypothesis is that FTFY-919 formula granules are non-inferior to the traditional decoction, with a non-inferiority margin of 0.2 in uw-mRS score; the placebo arm serves as an additional reference. Key secondary outcomes include neurological function, hematoma and perihematomal edema volumes, death or severe disability, health-related quality of life, TCM syndrome score, activities of daily living, recurrent or symptomatic ICH, and safety outcomes. Follow-up visits are scheduled at Day 7, Day 14, Day 28 and Day 90 after randomization. Enrollment is planned to start in September 2026 at five centers in China, with primary completion anticipated in November 2027 and study completion in January 2028.
Interventions
DRUGHuayu Jiedu Formula (FTFY-919) Granules
Huayu Jiedu Formula (FTFY-919) Chinese medicine formula granules containing Radix Ginseng Rubra 30 g, Radix Notoginseng 30 g and Radix et Rhizoma Rhei 5 g per dose. 14.5 g per sachet, one sachet three times daily for 28 consecutive days, first dose within 48 hours of symptom onset, dissolved in 100 mL warm water, administered orally or via nasogastric tube. Manufactured by Guangdong Yifang Pharmaceutical Co., Ltd.
DRUGHuayu Jiedu Formula (FTFY-919) Traditional Decoction
Traditional decoction of Huayu Jiedu Formula (FTFY-919) containing Radix Ginseng Rubra 30 g (concentrated decoction), Radix Notoginseng 30 g (15 g concentrated decoction plus 15 g powder) and Radix et Rhizoma Rhei 5 g (powder) per dose. Decoction is concentrated into granules with identical appearance and packaging to the formula granules; same dosage and regimen (14.5 g three times daily for 28 days). Manufactured by Guangdong Yifang Pharmaceutical Co., Ltd.
DRUGPlacebo Granules
Placebo granules prepared from non-bioactive food additives in accordance with the T/CACM 1420-2022 standard for placebo simulation of Chinese patent medicines. Identical appearance, packaging, dosage and regimen to the active treatment (14.5 g three times daily for 28 days).
Sponsors
Guangzhou University of Traditional Chinese Medicine
Guangdong Provincial Natural Science Foundation Management Committee
Guangdong Provincial Hospital of Traditional Chinese Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, care providers, investigators and outcome assessors are blinded. Granules, decoction-derived granules and placebo have identical appearance and packaging.
Intervention model description
Three-arm, 1:1:1 randomized trial: FTFY-919 formula granules, FTFY-919 traditional decoction, or placebo granules, in addition to standard Western medicine treatment.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 40 years; * Spontaneous intracerebral hemorrhage (ICH) confirmed by neuroimaging; * Hematoma volume 15-60 mL; * Within 48 hours of symptom onset (if onset time is unknown, the time last seen normal is used); * Meeting one of the following: basal ganglia or lobar hemorrhage with NIHSS score ≥ 8; or thalamic, brainstem or cerebellar hemorrhage with Glasgow Coma Scale (GCS) score 7-14; * Written informed consent obtained from the patient or the legal representative.
Exclusion criteria
* ICH secondary to structural brain abnormalities (including but not limited to cerebral vascular malformation, intracranial aneurysm, malignant tumor, moyamoya disease, trauma and prior ischemic stroke), cerebral amyloid angiopathy, thrombolysis or thrombectomy, anticoagulant therapy, antiplatelet therapy, or other secondary causes; * Patients judged by the responsible physician unlikely to benefit from the trial (e.g., advanced dementia) or at very high risk of early death, or other conditions considered unsuitable by the investigator; * Conditions that may interfere with follow-up or outcome assessment (e.g., significant pre-stroke disability with modified Rankin Scale score 3-5, end-stage malignant tumor, renal failure); * Known contraindications to Chinese medicine; * Pregnancy or breastfeeding; * Participation in another clinical trial that may interfere with the evaluation of this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Utility-weighted modified Rankin Scale (uw-mRS) score at Day 90 | Day 90 (± 7 days) after randomization | Modified Rankin Scale assessed at Day 90, converted to utility-weighted scores (weights: mRS 0 = 1.0, 1 = 0.91, 2 = 0.76, 3 = 0.65, 4 = 0.33, 5 = 0, 6 = 0). Primary comparison: FTFY-919 formula granules versus traditional decoction (non-inferiority, margin 0.2); placebo arm serves as an additional reference. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Any recurrent intracerebral hemorrhage or symptomatic intracerebral hemorrhage | During the 28-day treatment period | Occurrence of any recurrent intracerebral hemorrhage (ICH) or symptomatic ICH (sICH) during the 28-day treatment period. |
| Stroke Traditional Chinese Medicine (TCM) syndrome score | Day 14, Day 28 and Day 90 after randomization | TCM syndrome score of stroke assessed using the stroke TCM syndrome scale at Day 14, Day 28 and Day 90; response classified as cured, markedly effective, effective or ineffective based on percentage reduction of the score. |
| National Institutes of Health Stroke Scale (NIHSS) score | Day 7 and Day 14 after randomization | Neurological deficit assessed by the National Institutes of Health Stroke Scale at Day 7 and Day 14; higher scores indicate more severe neurological impairment. |
| Hematoma volume on head CT | Day 7 and Day 14 after randomization | Intracerebral hematoma volume measured by head CT using the multi-slice (Tada) formula at Day 7 and Day 14. |
| Perihematomal edema volume on head CT | Day 7 and Day 14 after randomization | Perihematomal edema volume assessed by head CT at Day 7 and Day 14 after randomization. |
| Death or severe disability (modified Rankin Scale 3-6) at Day 90 | Day 90 after randomization | Proportion of participants with death or severe disability, defined as modified Rankin Scale score of 3 to 6, at Day 90. |
| All-cause death at Day 90 | Day 90 after randomization | All-cause mortality within 90 days after randomization. |
| Severe disability (modified Rankin Scale 3-5) at Day 90 | Day 90 after randomization | Proportion of participants with severe disability, defined as modified Rankin Scale score of 3 to 5, at Day 90. |
| Health-related quality of life (EQ-5D-5L) at Day 90 | Day 90 after randomization | European Quality of Life 5-Dimensions 5-Level (EQ-5D-5L) questionnaire assessed at Day 90 to evaluate health-related quality of life. |
| Barthel Index (activities of daily living) at Day 14 and Day 90 | Day 14 and Day 90 after randomization | Barthel Index (ADL scale) assessed at Day 14 and Day 90; higher scores indicate better independence in activities of daily living. |
| Adverse events, serious adverse events and adverse events of special interest | Up to Day 14 after randomization | Safety assessed by adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI: hematoma expansion, new intracerebral hemorrhage, diarrhea, laboratory abnormalities including blood routine, liver and kidney function, coagulation, fecal occult blood and urinalysis) recorded up to Day 14. |
Contacts
CONTACTJianwen Guo, MD
PRINCIPAL_INVESTIGATORJianwen Guo, MD
Guangdong Provincial Hospital of Traditional Chinese Medicine
Outcome results
None listed