Back to resultsReducing Edema After intraCerebral Hemorrhage
Primary Purpose
Edema Brain
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Sodium Aescinate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Edema Brain focused on measuring edema, intracerebral hemorrhage, sodium aescinate
Eligibility Criteria
Inclusion Criteria:
- Patients aged between 18-80 years old;
- Spontaneous ICH confirmed by cranial CT;
- Time from onset to randomization within 24 hours;
- Superatentorial ICH;
- Hematoma volume between 10-30 ml (calculated using ABC/2 method);
- Glasgow coma scale (GCS) > 9 on admission;
- informed and consent.
Exclusion Criteria:
- 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);
- ICH secondary to trauma；
- Primary intraventricular hemorrhage (IVH);
- Signs of herniation, such as progressive decline in consciousness, decreased or disappearance of pupillary light reflection, bilateral pyramidal tract signs, etc;
- Other serious, advanced or terminal illness such that life expectancy is less than one year (e.g. advanced metastatic cancer);
- Severe cardiac insufficiency (NYHA class III or IV);
- High-risk arrhythmia, such as sick sinus syndrome, second or third degree atrioventricular block, bradycardia-related syncope without a pacemaker, etc;
- 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;
- Severe renal insufficiency: Severe renal insufficiency is defined as creatinine greater than 1.5 times the upper limit of normal;
- History of severe asthma or chronic obstructive pulmonary disease (COPD);
- History of coagulopathy or systemic bleeding;
- A thrombocyte count below <100 x 10^9/L or leukocytosis < 2 x 10^9/L on admission;
- 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;
- Patients with preexisting disability of a modified Rankin Scale (mRS) score greater than 2 prior to ICH;
- Unable to understand the research procedures and/or complete follow-up due to mental illness, cognitive impairment, affective disorder, etc;
- Women of childbearing potential, pregnant, or breastfeeding at randomization;
- Contraindication to sodium aescinate；
- Participate in other clinical studies within 3 months or are participating in other clinical studies.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
sodium aescinate group
placebo group
Arm Description
Trial treatment is administered as sodium Aescinate 10mg in 250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.
Trial treatment is administered as 250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.
Outcomes
Primary Outcome Measures
Absolute edema volume on day 14 after ICH
Absolute edema volume is based on brain CT image
Secondary Outcome Measures
Relative edema volume on day 14 after ICH
Relative edema volume is based on edema volume divided by hematoma volume
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
Cytotoxic edema on 72 ±12 hour after ICH symptom onset
Cytotoxic edema is based on brain MRI image
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
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
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
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
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
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
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
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.）
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. ）
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.）
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.）
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）
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. ）
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.）
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.
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.
Full Information
NCT ID
NCT05263167
First Posted
January 9, 2022
Last Updated
March 6, 2022
Sponsor
Beijing Tiantan Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05263167
Brief Title
Reducing Edema After intraCerebral Hemorrhage
Official Title
Reducing Edema After intraCerebral Hemorrhage
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 15, 2022 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Tiantan Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Edema Brain
Keywords
edema, intracerebral hemorrhage, sodium aescinate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
sodium aescinate group
Arm Type
Experimental
Arm Description
Trial treatment is administered as sodium Aescinate 10mg in 250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.
Arm Title
placebo group
Arm Type
Placebo Comparator
Arm Description
Trial treatment is administered as 250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.
Intervention Type
Drug
Intervention Name(s)
Sodium Aescinate
Other Intervention Name(s)
Sodium Aescinate for Injection
Intervention Description
sodium Aescinate 10mg in 250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
0.9% sodium chloride injection
Intervention Description
250ml sodium chloride 0.9% infusion bag intravenously once daily for 10 days.
Primary Outcome Measure Information:
Title
Absolute edema volume on day 14 after ICH
Description
Absolute edema volume is based on brain CT image
Time Frame
on day 14 after ICH
Secondary Outcome Measure Information:
Title
Relative edema volume on day 14 after ICH
Description
Relative edema volume is based on edema volume divided by hematoma volume
Time Frame
on day 14 after ICH
Title
Absolute edema volume and relative edema volume on 24 ±12 hour and 72±12 hour after ICH symptom onset
Description
absolute edema volume is based on brain CT image；relative edema volume is based on edema volume divided by hematoma volume
Time Frame
on 24±12 hour and 72±12 hour after ICH symptom onset
Title
Cytotoxic edema on 72 ±12 hour after ICH symptom onset
Description
Cytotoxic edema is based on brain MRI image
Time Frame
on 72 ±12 hour after ICH symptom onset
Title
Dynamic changes of serum IL-x levels(ng/ml) within 14 days of symptom onset
Description
The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset
Time Frame
within 14 days of symptom onset
Title
Dynamic changes of serum NF-kB levels(ug/ml) within 14 days of symptom onset
Description
The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset
Time Frame
within 14 days of symptom onset
Title
Dynamic changes of serum TNF levels(ng/ml) within 14 days of symptom onset
Description
The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset
Time Frame
within 14 days of symptom onset
Title
Dynamic changes of serum MMPs levels(ug/ml) within 14 days of symptom onset
Description
The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset
Time Frame
within 14 days of symptom onset
Title
Dynamic changes of serum VEGF levels(pg/ml) within 14 days of symptom onset
Description
The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset
Time Frame
within 14 days of symptom onset
Title
Dynamic changes of serum EPO levels(ng/ml) within 14 days of symptom onset
Description
The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset
Time Frame
within 14 days of symptom onset
Title
Dynamic changes of serum angiopoietin-1 levels(pg/ml) within 14 days of symptom onset
Description
The purpose is to evaluate dynamic changes of serum inflammatory factor levels within 14 days of symptom onset
Time Frame
within 14 days of symptom onset
Title
Change of neurological dysfunction within 14 days of symptom onset
Description
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.）
Time Frame
within 14 days of symptom onset
Title
Cognition（MMSE) at 14 days of symptom onset
Description
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. ）
Time Frame
at 14 days of symptom onset
Title
Cognition（MoCA) at 14 days of symptom onset
Description
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.）
Time Frame
at 14 days of symptom onset
Title
Dependency at 90±7 days after onset
Description
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.）
Time Frame
at 90±7 days after onset
Title
Quality of life at 90±7 days after onset
Description
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）
Time Frame
at 90±7 days after onset
Title
Cognition（MMSE） at 90±7 days after onset
Description
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. ）
Time Frame
at 90±7 days after onset
Title
Cognition（MoCA） at 90±7 days after onset
Description
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.）
Time Frame
at 90±7 days after onset
Title
adverse events(AEs) and serious adverse events（SAEs) through 14 days
Description
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.
Time Frame
up to 14 days
Title
all serious adverse events(SAEs) throughout the study follow-up period up to 3 months
Description
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.
Time Frame
up to 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients aged between 18-80 years old;
Spontaneous ICH confirmed by cranial CT;
Time from onset to randomization within 24 hours;
Superatentorial ICH;
Hematoma volume between 10-30 ml (calculated using ABC/2 method);
Glasgow coma scale (GCS) > 9 on admission;
informed and consent.
Exclusion Criteria:
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);
ICH secondary to trauma；
Primary intraventricular hemorrhage (IVH);
Signs of herniation, such as progressive decline in consciousness, decreased or disappearance of pupillary light reflection, bilateral pyramidal tract signs, etc;
Other serious, advanced or terminal illness such that life expectancy is less than one year (e.g. advanced metastatic cancer);
Severe cardiac insufficiency (NYHA class III or IV);
High-risk arrhythmia, such as sick sinus syndrome, second or third degree atrioventricular block, bradycardia-related syncope without a pacemaker, etc;
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;
Severe renal insufficiency: Severe renal insufficiency is defined as creatinine greater than 1.5 times the upper limit of normal;
History of severe asthma or chronic obstructive pulmonary disease (COPD);
History of coagulopathy or systemic bleeding;
A thrombocyte count below <100 x 10^9/L or leukocytosis < 2 x 10^9/L on admission;
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;
Patients with preexisting disability of a modified Rankin Scale (mRS) score greater than 2 prior to ICH;
Unable to understand the research procedures and/or complete follow-up due to mental illness, cognitive impairment, affective disorder, etc;
Women of childbearing potential, pregnant, or breastfeeding at randomization;
Contraindication to sodium aescinate；
Participate in other clinical studies within 3 months or are participating in other clinical studies.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hao Feng
Phone
13811059362
Email
fenghao57865578@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ji
Organizational Affiliation
Beijing Tiantan Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Reducing Edema After intraCerebral Hemorrhage
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