Chinese Herbal Medicine in Acute INtracerebral Haemorrhage (CHAIN) Trial

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: Chinese herbal medicine FYTF-919

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1504
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jianwen Guo, MD; Phone Number: +86-13724899379; Email: jianwen_guo@qq.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Guangdong Provincial Hospital of Chinese Medicine
      • Contact: Jianwen Guo, MD; Phone Number: +86 13724899379; Email: jianwen_guo@qq.com
      • Contact: Lily Song, PhD; Phone Number: +86 13916466400; Email: lsong@georgeinstitute.org.cn
      • Principal Investigator: Jianwen Guo
      • Principal Investigator: Craig Anderson, The George Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; 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)	Drug: 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); Other Names: Chinese herbal medicine
Placebo Comparator: Control group; Placebo treatment: Oral liquid 33ml TID (or patients who are unconscious or dysphagia, a dose of 25ml * Q6H will be given through nasal feeding)	Drug: 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); Other Names: Chinese herbal medicine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Utility-weighted modified Rankin scale scores	Utility-weighted modified Rankin scale scores. The value range from 0 to 10: higher scores mean a better outcome.	90 days after the treatment started

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Utility-weighted mRS scores	Utility-weighted modified Rankin scale scores. The value range from 0 to 10: higher scores mean a better outcome.	180 days after the treatment started
7 levels of mRS	Ordinal analysis of 7 levels of mRS. The value range 0-6: higher scores mean a worse outcome.	28 days, 90 days and 180 days after the treatment started
Poor prognosis rate	Binary variable: 1 means mRS 4-6 points; 0 means mRS is 0-3 points.	28 days, 90 days and 180 days after the treatment started
NIHSS score	National Institute of Health Stroke Scale Score. The value range 0-42: higher scores mean a worse outcome.	7 days and 28 days after the treatment started
Mortality rate	Mortality rate	28 days, 90 days and 180 days
Discharge rate	Discharge rate	28 days after the treatment started
European Quality of Life 5-dimensional questionnaire (EQ-5D-5L)	The EQ-5D comprises five dimensions of health: mobility, ability to self-care, ability to undertake usual activities, pain and discomfort, and anxiety and depression. . EQ-5D-5L, includes five levels of severity for each dimension (no problems, slight problems, moderate problems, severe problems, and extreme problems). The value range 0-100: higher scores mean a worse outcome.	28 days, 90 days and 180 days after the treatment started
BI	Barthel index. The value range 0-100: higher scores mean a better outcome.	28 days, 90 days and 180 days after the treatment started
The cerebral edema volume	The cerebral edema volume	Baseline, 24 hours, 7 days, 14 days or at discharge
The hematoma volume	The hematoma volume	Baseline, 24 hours, 7 days, 14 days or discharge
SAP	The incidence of stroke-associated pneumonia patients	Baseline, 24 hours, 7 days, 14 days or discharge
CPIS	Clinical pulmonary infection score. The value range 0-12: higher scores mean a worse outcome.	The onset of SAP, 3 days and 7 days after the occurrence of SAP
Pulmonary infection	Diagnosed by using the 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	The onset of SAP, 3 days and 7 days after the occurrence of SAP
Antibiotic usage	Antibiotic usage among patients with SAP	The onset of SAP, 3 days and 7 days after the occurrence of SAP

Collaborators and Investigators

• Sponsor: Guangzhou University of Traditional Chinese Medicine
• Collaborators: The George Institute
• Investigators: Principal Investigator: Craig Anderson, MD, The George Institute for Global Health, Australia

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 24, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: September 24, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Stroke; Clinical trial; Chinese herbal medicine; Functional recovery; Intracerebral haemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: 2020B1111100009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data can be shared with bona fide researchers after the publication of the main results, based on a submitted protocol to the research office of The George Institute for Global Health, Sydney Australia.
• IPD Sharing Time Frame: Data sharing will be available from 12 months after the publication of the main results.
• IPD Sharing Access Criteria: The data sharing will be only for the purposes of health and medical research and within the constraints of the consent under which the data were originally gathered.; The Custodian of the Collection will not consider any Proposals for data sharing that unblind, or potentially unblind, randomised comparisons in active / ongoing trials.; Requesters should be employees of a recognised academic institution, health service organisation, commercial research organisation or from the pharmaceutical industry. Requesters must have experience in medical research.; Requesters must be able to demonstrate through their peer review publications in the area of interest their ability to carry out the proposed use of the requested dataset from a Collection.; The Requesters must not have a conflict of interest that may potentially influence their interpretation of any analyses.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No