Chinese Herbal Medicine in Acute INtracerebral Haemorrhage (CHAIN) Trial

Guangzhou University of Traditional Chinese Medicine

Status and phase: Not yet enrolling; Phase 3

Conditions: Intracerebral Hemorrhage

Treatments: Drug: Chinese herbal medicine FYTF-919

Study type: Interventional

Funder types: Other

Identifiers

NCT05066620

2020B1111100009

Details and patient eligibility

About

TCM is an essential context of the ICH management in Chinese culture. Given the potential benefits of Chinese herbal medicine FYTF-919 in reducing haematoma and bleeding after acute ICH from fundamental research and small clinical studies, more reliable evidence is required to guide ICH treatment using TCM. This study aims to determine the effectiveness and safety of TCM in a larger sample of patients with moderate-severe ICH and provide evidence for TCM clinical guidelines on ICH management. The presumed mechanism of action is in promoting the reabsorption of the haematoma and perihematomal oedema in ICH.

Full description

A multicentre, prospective, randomised, double-blind, placebo-controlled trial to be conducted through hospital network of investigators in China. A total of 1504 patients with ICH will be recruited from approximately 20-30 hospitals. Randomised is via a central internet-based system according to block random grouping method stratified by site, neurological severity NIHSS <15 vs ≥15), and haematoma location (basal ganglia + lobe vs thalamus + cerebellum + brain stem + ventricle) to ensure balance in key prognostic factors. Endpoint assessment will be blinded to treatment allocation. The primary aim of this study is to determine the effectiveness and safety of a Chinese herbal medicine FYTF-919 as compared to placebo on functional recovery according to Utility-weighted modified Rankin scale (UW-mRS) at 90 days after acute ICH. Secondary aims include examining whether the Chinese herbal medicine FYTF-919 leads to positive treatment effect on: 1) Utility-weighted mRS scores at 180 days; 2)Ordinal analysis of 7 levels of mRS at 28 days, 90 days and 180 days; 3) Poor prognosis, defined as mRS 4-6 points at 28 days, 90 days and 180 days; 4) NIHSS score at 7 days and 28 days; 5) Mortality rate at 28 days, 90 days and 180 days; 6) Discharge rate at 28 days; 7) EQ-5D-5L at 28days, 90 days and 180 days; 8) BI at 28 days, 90 days and 180 days; 9) The cerebral edema volume at baseline, 24 hours, 7 days, 14 days or at discharge; 10) The hematoma volume at baseline, 24 hours, 7 days, 14 days or discharge; 11) The incidence of stroke-associated pneumonia (SAP) patients; 12) Clinical pulmonary infection score (CIPS) at the onset of SAP, 3 days, and 7 days, after the occurrence of SAP; 13) Chest imaging (DR/CT), body temperature, white blood cell count, C-reactive protein (CRP), procalcitonin (PCT) blood gas analysis, and sputum culture/airway aspirate culture at the onset of SAP, 3 days, and 7 days after the occurrence of SAP; 14) Antibiotic usage among patients with SAP.

Enrollment: 1,504 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥18 years;
2. Diagnosis of spontaneous ICH, confirmed by brain imaging;
3. Presentation within 48 hours of symptom onset (or last seen well);
4. Meet any of the following criteria: a) NIHSS ≥8, or b) GCS 7-14;
5. Provide written informed consent by patient (or approved surrogate);

Exclusion criteria

1. ICH secondary to a structural abnormality in the brain (e.g. cerebrovascular malformation, arterial aneurysm, tumour, Moyamoya disease, trauma, or previous ischaemic stroke), or secondary to presumed cerebrovascular amyloidosis, or secondary to reperfusion treatment for ischaemic stroke, or secondary to anticoagulant treatment, or secondary to antiplatelet treatment.
2. Unlikely to potentially benefit from therapy (e.g. advanced dementia) or judged by responsible treating clinician to have a high likelihood of early death irrespective of treatment;
3. Other medical illness that will interfere with outcome assessments and follow-up (e.g. known significant pre-stroke disability [modified Rankin scale {mRS} scores 4-5], advanced cancer and renal failure);
4. Known definite contraindication to the Chinese herbal medicine;
5. Women who are known to be pregnant or lactating;
6. Currently participating in another trial which would interfere with outcome assessments.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,504 participants in 2 patient groups, including a placebo group

Intervention group

Experimental group

Description:

Chinese herbal medicine FYTF-919: Oral liquid 33ml TID (for patients who are unconscious or dysphagia, a dose of 25ml \* Q6H will be given through nasal feeding)

Treatment:

Drug: Chinese herbal medicine FYTF-919

Control group

Placebo Comparator group

Description:

Placebo treatment: Oral liquid 33ml TID (or patients who are unconscious or dysphagia, a dose of 25ml \* Q6H will be given through nasal feeding)

Treatment:

Drug: Chinese herbal medicine FYTF-919