Reducing Edema After intraCerebral Hemorrhage

The REACH trial is a prospective multicenter double-blind randomized placebo-controlled trial with blinded end-point adjudication. Participants are randomized (1:1) to receive either sodium aescinate or matching placebo (0.9% saline). The primary outcome is the absolute volume of PHE evaluated based on brain CT image on day 14 after ICH.

Study Overview

• Status: Not yet recruiting
• Conditions: Edema Brain
• Intervention / Treatment: Drug: Sodium Aescinate; Drug: Placebo

Detailed Description

The REACH trial is a prospective multicenter double-blind randomized placebo-controlled trial with blinded end-point adjudication. Participants are randomized (1:1) to receive either sodium aescinate or matching placebo (0.9% saline). The primary outcome is the absolute volume of PHE evaluated based on brain CT image on day 14 after ICH. Functional outcome is assessed face to face at 3-month after onset. Meanwhile, central telephone follow-up determines functional outcomes at 3-month after onset. Brain imaging (CT) is performed as part of routine care prior to enrolment. A research CT scan is performed after 24h of symptom onset to assess hematoma expansion; a second research CT scan is performed at 72 hours after onset to assess brain swelling and dynamic change of PHE. The study was approved by the ethics committee of the Beijing Tiantan hospital. The study is conducted according to GCP guidelines.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hao Feng; Phone Number: 13811059362; Email: fenghao57865578@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged between 18-80 years old;
2. Spontaneous ICH confirmed by cranial CT;
3. Time from onset to randomization within 24 hours;
4. Superatentorial ICH;
5. Hematoma volume between 10-30 ml (calculated using ABC/2 method);
6. Glasgow coma scale (GCS) > 9 on admission;
7. informed and consent.

Exclusion Criteria:

1. Suspected secondary cause of ICH (e.g. aneurysm, vascular malformation, neoplasia, cerebral venous thrombosis, hemorrhagic transformation of recent ischemic stroke, thrombolysis or endovascular treatment, anticoagulation, et al);
2. ICH secondary to trauma；
3. Primary intraventricular hemorrhage (IVH);
4. Signs of herniation, such as progressive decline in consciousness, decreased or disappearance of pupillary light reflection, bilateral pyramidal tract signs, etc;
5. Other serious, advanced or terminal illness such that life expectancy is less than one year (e.g. advanced metastatic cancer);
6. Severe cardiac insufficiency (NYHA class III or IV);
7. High-risk arrhythmia, such as sick sinus syndrome, second or third degree atrioventricular block, bradycardia-related syncope without a pacemaker, etc;
8. Severe liver insufficiency; severe liver insufficiency is defined as ALT > 2 times the upper limit of normal or AST greater than 2 times the upper limit of normal;
9. Severe renal insufficiency: Severe renal insufficiency is defined as creatinine greater than 1.5 times the upper limit of normal;
10. History of severe asthma or chronic obstructive pulmonary disease (COPD);
11. History of coagulopathy or systemic bleeding;
12. A thrombocyte count below <100 x 10^9/L or leukocytosis < 2 x 10^9/L on admission;
13. Patients who plan to undergo surgical intervention before the first administration, including but not limited to hematoma removal (including minimally invasive and conventional surgery), decompressive craniectomy, hematoma aspiration, and ventricular puncture external drainage;
14. Patients with preexisting disability of a modified Rankin Scale (mRS) score greater than 2 prior to ICH;
15. Unable to understand the research procedures and/or complete follow-up due to mental illness, cognitive impairment, affective disorder, etc;
16. Women of childbearing potential, pregnant, or breastfeeding at randomization;
17. Contraindication to sodium aescinate；
18. Participate in other clinical studies within 3 months or are participating in other clinical studies.

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: sodium aescinate group; Trial treatment is administered as sodium Aescinate 10mg in 250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.	Drug: Sodium Aescinate; sodium Aescinate 10mg in 250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.; Other Names: Sodium Aescinate for Injection
Placebo Comparator: placebo group; Trial treatment is administered as 250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.	Drug: Placebo; 250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.; Other Names: 0.9% sodium chloride injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute edema volume on day 14 after ICH	Absolute edema volume is based on brain CT image	on day 14 after ICH

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative edema volume on day 14 after ICH	Relative edema volume is based on edema volume divided by hematoma volume	on day 14 after ICH
Absolute edema volume and relative edema volume on 24 ±12 hour and 72±12 hour after ICH symptom onset	absolute edema volume is based on brain CT image；relative edema volume is based on edema volume divided by hematoma volume	on 24±12 hour and 72±12 hour after ICH symptom onset
Cytotoxic edema on 72 ±12 hour after ICH symptom onset	Cytotoxic edema is based on brain MRI image	on 72 ±12 hour after ICH symptom onset
Dynamic changes of serum IL-x levels(ng/ml) within 14 days of symptom onset	The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset	within 14 days of symptom onset
Dynamic changes of serum NF-kB levels(ug/ml) within 14 days of symptom onset	The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset	within 14 days of symptom onset
Dynamic changes of serum TNF levels(ng/ml) within 14 days of symptom onset	The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset	within 14 days of symptom onset
Dynamic changes of serum MMPs levels(ug/ml) within 14 days of symptom onset	The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset	within 14 days of symptom onset
Dynamic changes of serum VEGF levels(pg/ml) within 14 days of symptom onset	The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset	within 14 days of symptom onset
Dynamic changes of serum EPO levels(ng/ml) within 14 days of symptom onset	The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset	within 14 days of symptom onset
Dynamic changes of serum angiopoietin-1 levels(pg/ml) within 14 days of symptom onset	The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset	within 14 days of symptom onset
Change of neurological dysfunction within 14 days of symptom onset	Change of neurological dysfunction within 14 days of symptom onset is based on National institute of health stroke scale(NIHSS）14d-NIHSS enrollment.（The minimum and maximum values of NIHSS is 0 and 42,respectively, higher scores mean a worse outcome.）	within 14 days of symptom onset
Cognition（MMSE) at 14 days of symptom onset	Cognition is based on Mini-mental State Examination（MMSE）. （The minimum and maximum values of MMSE is 0 and 30,respectively, higher scores mean a better outcome. ）	at 14 days of symptom onset
Cognition（MoCA) at 14 days of symptom onset	Cognition is based on Montreal Cognitive Assessment（MoCA）. （The minimum and maximum values of MoCA is 0 and 30,respectively, higher scores mean a better outcome.）	at 14 days of symptom onset
Dependency at 90±7 days after onset	Dependency at 90±7 days after onset Dependency is based on Modified Rankin Scale（mRS ）. （The minimum and maximum values of mRS is 0 and 5,respectively, higher scores mean a worse outcome.）	at 90±7 days after onset
Quality of life at 90±7 days after onset	Quality of Life is based on five-level version of EuroQol Five Dimensions Questionnaire（EQ-5D-5L）. （The scale mainly contains 5 dimensions, including mobility, self-care ability, ability to perform daily activities, pain or discomfort, and anxiety or depression. Each dimension is divided into 5 levels: no difficulty, mild difficulty, moderate difficulty, severe difficulty, extreme difficulty or inability）	at 90±7 days after onset
Cognition（MMSE） at 90±7 days after onset	Cognition is based on Mini-mental State Examination（MMSE）. （The minimum and maximum values of MMSE is 0 and 30,respectively, higher scores mean a better outcome. ）	at 90±7 days after onset
Cognition（MoCA） at 90±7 days after onset	Cognition is based on Montreal Cognitive Assessment（MoCA）. （The minimum and maximum values of MoCA is 0 and 30,respectively, higher scores mean a better outcome.）	at 90±7 days after onset
adverse events(AEs) and serious adverse events（SAEs) through 14 days	Any complications associated with sodium aescinate treatment (e.g. allergy, gastrointestinal complications, bleedings, thrombotic, or infectious complications) were defined as adverse events (AEs). SAEs are defined as any untoward medical occurrence or effect that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity. SAEs and safety endpoints are reported in line with expedited reporting regulations and then adjudicated by an independent panel.	up to 14 days
all serious adverse events(SAEs) throughout the study follow-up period up to 3 months	SAEs are defined as any untoward medical occurrence or effect that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity.	up to 3 months

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Ji, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 15, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): March 31, 2025

Study Registration Dates

• First Submitted: January 9, 2022
• First Submitted That Met QC Criteria: February 21, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 21, 2022
• Last Update Submitted That Met QC Criteria: March 6, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: edema; intracerebral hemorrhage; sodium aescinate
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Edema; Cerebral Hemorrhage
• Other Study ID Numbers: 100999

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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