Clinical trial NCT05263167: Reducing Edema After intraCerebral Hemorrhage
Official title: Reducing Edema After intraCerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Edema Brain
Keywords: edema
intracerebral hemorrhage
sodium aescinate
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2022-03-02
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Absolute edema volume on day 14 after ICH
timeFrame: on day 14 after ICH
Secondary outcomes:
measure: Relative edema volume on day 14 after ICH
timeFrame: on day 14 after ICH
measure: Absolute edema volume and relative edema volume on 24 ±12 hour and 72±12 hour after ICH symptom onset
timeFrame: on 24±12 hour and 72±12 hour after ICH symptom onset
measure: Cytotoxic edema on 72 ±12 hour after ICH symptom onset
timeFrame: on 72 ±12 hour after ICH symptom onset
measure: Dynamic changes of serum IL-x levels(ng/ml) within 14 days of symptom onset
timeFrame: within 14 days of symptom onset
measure: Dynamic changes of serum NF-kB levels(ug/ml) within 14 days of symptom onset
timeFrame: within 14 days of symptom onset
measure: Dynamic changes of serum TNF levels(ng/ml) within 14 days of symptom onset
timeFrame: within 14 days of symptom onset
measure: Dynamic changes of serum MMPs levels(ug/ml) within 14 days of symptom onset
timeFrame: within 14 days of symptom onset
measure: Dynamic changes of serum VEGF levels(pg/ml) within 14 days of symptom onset
timeFrame: within 14 days of symptom onset
measure: Dynamic changes of serum EPO levels(ng/ml) within 14 days of symptom onset
timeFrame: within 14 days of symptom onset
measure: Dynamic changes of serum angiopoietin-1 levels(pg/ml) within 14 days of symptom onset
timeFrame: within 14 days of symptom onset
measure: Change of neurological dysfunction within 14 days of symptom onset
timeFrame: within 14 days of symptom onset
measure: Cognition（MMSE) at 14 days of symptom onset
timeFrame: at 14 days of symptom onset
measure: Cognition（MoCA) at 14 days of symptom onset
timeFrame: at 14 days of symptom onset
measure: Dependency at 90±7 days after onset
timeFrame: at 90±7 days after onset
measure: Quality of life at 90±7 days after onset
timeFrame: at 90±7 days after onset
measure: Cognition（MMSE） at 90±7 days after onset
timeFrame: at 90±7 days after onset
measure: Cognition（MoCA） at 90±7 days after onset
timeFrame: at 90±7 days after onset
measure: adverse events(AEs) and serious adverse events（SAEs) through 14 days
timeFrame: up to 14 days
measure: all serious adverse events(SAEs) throughout the study follow-up period up to 3 months
timeFrame: up to 3 months
Other outcomes:
Locations:
Study officials:
affiliation: Beijing Tiantan Hospital
name: Ji
role: PRINCIPAL_INVESTIGATOR
References: