Clinical trial NCT05066620: Chinese Herbal Medicine in Acute INtracerebral Haemorrhage (CHAIN) Trial
Official title: An Investigator-initiated and Conducted Multicentre, Prospective, Randomised, Double-blinded Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Chinese Herbal Medicine in Patients With Acute Intracerebral Haemorrhage
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Intracerebral Hemorrhage
Keywords: Intracerebral haemorrhage
Functional recovery
Chinese herbal medicine
Stroke
Clinical trial
Lead sponsor: Guangzhou University of Traditional Chinese Medicine
Sponsor class: OTHER
Collaborators: name: The George Institute
First posted: 2021-10-04
Enrollment: 1504
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Utility-weighted modified Rankin scale scores
timeFrame: 90 days after the treatment started
Secondary outcomes:
measure: Utility-weighted mRS scores
timeFrame: 180 days after the treatment started
measure: 7 levels of mRS
timeFrame: 28 days, 90 days and 180 days after the treatment started
measure: Poor prognosis rate
timeFrame: 28 days, 90 days and 180 days after the treatment started
measure: NIHSS score
timeFrame: 7 days and 28 days after the treatment started
measure: Mortality rate
timeFrame: 28 days, 90 days and 180 days
measure: Discharge rate
timeFrame: 28 days after the treatment started
measure: European Quality of Life 5-dimensional questionnaire (EQ-5D-5L)
timeFrame: 28 days, 90 days and 180 days after the treatment started
measure: BI
timeFrame: 28 days, 90 days and 180 days after the treatment started
measure: The cerebral edema volume
timeFrame: Baseline, 24 hours, 7 days, 14 days or at discharge
measure: The hematoma volume
timeFrame: Baseline, 24 hours, 7 days, 14 days or discharge
measure: SAP
timeFrame: Baseline, 24 hours, 7 days, 14 days or discharge
measure: CPIS
timeFrame: The onset of SAP, 3 days and 7 days after the occurrence of SAP
measure: Pulmonary infection
timeFrame: The onset of SAP, 3 days and 7 days after the occurrence of SAP
measure: Antibiotic usage
timeFrame: The onset of SAP, 3 days and 7 days after the occurrence of SAP
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial Hospital of Chinese Medicine
state: Guangdong
Study officials:
affiliation: The George Institute for Global Health, Australia
name: Craig Anderson, MD
role: PRINCIPAL_INVESTIGATOR
References: