Back to resultsRemote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage (RICH-2)
Primary Purpose
Intracerebral Hemorrhage, Acute Stroke
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Remote ischemic conditioning
Sham remote ischemic conditioning
Standard medication therapy
Sponsored by
About this trial
This is an interventional treatment trial for Intracerebral Hemorrhage focused on measuring Therapy, Neuroprotection
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 and ≤ 80 years
- The diagnosis of supratentorial ICH is confirmed by brain CT scan
- Hematoma volume of 10 to 30 ml and Glasgow Coma Score (GCS)>8 at randomization.
- National Institutes of Health Stroke Scale (NIHSS)≥6 and ≤20 points at randomization.
- Randomization and starting treatment between 24 and 48 hours of symptom ictus.
- Signed and dated informed consent is obtained.
Exclusion Criteria:
- Planned surgical evacuation of ICH prior to administration of investigational intervention
- ICH concomitant with subarachnoid hemorrhage or intraventricular hemorrhage
- Suspected secondary ICH related to tumor, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis
- Patients with a pre-existing neurological deficit (mRS>1) or psychiatric disease that would confound the neurological or functional evaluations.
- Coagulopathy - defined as elevated aPTT or INR >1.3 upon presentation; concurrent use of direct thrombin inhibitors (such as dabigatran), direct factor Xa inhibitors (such as rivaroxaban or apixaban), or low-molecular-weight heparin
- Severe renal disease (i.e., renal disorder requiring dialysis ) or eGFR <30ml/min/1.73m2
- Severe liver disorder, or ALT >3 times or bilirubin >2 times upper limit of normal
- Known severe hearing loss or cognitive impairment
- Known pregnancy, or positive pregnancy test, or breastfeeding
- Patients known or suspected of not being able to comply with the study protocol due to alcoholism, noncompliance or any other cause
- Life expectancy of less than 90 days due to co-morbid conditions
- Concurrent participation in another research protocol for investigation of another experimental therapy
- Severe, sustained hypertension (Systolic blood pressure> 180 mmHg or diastolic blood pressure> 110 mmHg).
- Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs.
- Any condition which, in the judgement of the investigator, might increase the risk to the patient.
Sites / Locations
- Xuanwu Hospital, Capital Medical University
- Beijing Red Cross Emergency Rescue Center
- Beijing Renhe Hospital
- Chengde Central HospitalRecruiting
- The Six People's Hospital of HengshuiRecruiting
- Nanshi Hospital of NanyangRecruiting
- Tongliao Municipal Hosptial
- The First People's Hospital of ChangzhouRecruiting
- The Affiliated Hospital of Xuzhou Medical UniversityRecruiting
- Tianjin Huanhu HospitalRecruiting
- Jiaxing Second Hospital
- Shaoxing People's HospitalRecruiting
- Zhuji People's Hospital of Zhejaing Province
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Intervention group
Sham group
Arm Description
Subjects in the intervention group will receive remote ischemic conditioning and standard background medical treatment.
Subjects in the placebo group will receive sham remote ischemic conditioning and standard background medical treatment alone.
Outcomes
Primary Outcome Measures
Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. The primary outcome measure is the mRS score, dichotomized to define favorable functional outcome as mRS 0-2 at 90 days.
Secondary Outcome Measures
Proportion of Patients With mRS Score 0-3 at 90 Days
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Another measure of efficacy is the mRS score, dichotomized to define good functional outcome as mRS 0-3 at 90 days.
Proportion of Patients With mRS Score 0-2 at 180 Days
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Another measure of efficacy is the mRS score, dichotomized to define good functional outcome as mRS 0-2 at 180 days.
Proportion of Patients With mRS Score 0-3 at 180 Days
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Another measure of efficacy is the mRS score, dichotomized to define good functional outcome as mRS 0-3 at 180 days.
Number of Subjects Experiencing Serious Adverse Events
Number of subjects experiencing Serious adverse events at any time from randomization through day 90
Number of Subjects With Serious Adverse Events Within 7 Days
Number of Subjects Experiencing Serious Adverse Events within 7 days of randomization
Full Information
NCT ID
NCT04657133
First Posted
December 1, 2020
Last Updated
July 16, 2022
Sponsor
Capital Medical University
1. Study Identification
Unique Protocol Identification Number
NCT04657133
Brief Title
Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage
Acronym
RICH-2
Official Title
The Safety and Efficacy of Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage: A Multicenter, Randomized, Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 22, 2021 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Capital Medical University
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
Intracerebral hemorrhage (ICH) results from the rupture of small vessels damaged by chronic hypertension, amyloid angiopathy or other disease. Currently, ICH has been a devastating type of stroke that lacking effective therapy. Remote ischemic conditioning (RIC), a systematically protective strategy, has been found to have neuroprotective effects by in patients with ischemic stroke. In addition, animal studies show that RIC is safe in ICH model and it could accelerate the absorption of hematoma. In a previous clinical study (RICH-1), RIC have been found to be safe and well-tolerated in patients with ICH. Therefore, the investigators plan to undertake this study to further evaluate the safety and efficacy of RIC in patients with ICH.
The investigators hypothesize that treatment with RIC will accelerate the absorption of hematoma and improve patients' functional outcomes. Results of this study can potentially bring into account new means to improve the outcomes of ICH patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracerebral Hemorrhage, Acute Stroke
Keywords
Therapy, Neuroprotection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
452 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention group
Arm Type
Experimental
Arm Description
Subjects in the intervention group will receive remote ischemic conditioning and standard background medical treatment.
Arm Title
Sham group
Arm Type
Placebo Comparator
Arm Description
Subjects in the placebo group will receive sham remote ischemic conditioning and standard background medical treatment alone.
Intervention Type
Device
Intervention Name(s)
Remote ischemic conditioning
Other Intervention Name(s)
RIC
Intervention Description
RIC is a non-invasive therapy that performed by an electric autocontrol device with cuff placed on arm. RIC procedures consist of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuff on one arm. The procedure will be performed once daily for consecutive 7 days after enrollment.
Intervention Type
Device
Intervention Name(s)
Sham remote ischemic conditioning
Other Intervention Name(s)
Sham RIC
Intervention Description
Sham RIC will be performed by the same electric autocontrol device with cuff placed on arm. Sham RIC procedures consist of five cycles of 5-min inflation (30 mmHg) and 5-min deflation of cuff on one arm. The procedure will be performed once daily for consecutive 7 days after enrollment.
Intervention Type
Drug
Intervention Name(s)
Standard medication therapy
Intervention Description
Standard medication therapy will be performed according to the national and international guidelines.
Primary Outcome Measure Information:
Title
Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days
Description
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. The primary outcome measure is the mRS score, dichotomized to define favorable functional outcome as mRS 0-2 at 90 days.
Time Frame
0-90 days.
Secondary Outcome Measure Information:
Title
Proportion of Patients With mRS Score 0-3 at 90 Days
Description
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Another measure of efficacy is the mRS score, dichotomized to define good functional outcome as mRS 0-3 at 90 days.
Time Frame
90 days
Title
Proportion of Patients With mRS Score 0-2 at 180 Days
Description
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Another measure of efficacy is the mRS score, dichotomized to define good functional outcome as mRS 0-2 at 180 days.
Time Frame
180 days
Title
Proportion of Patients With mRS Score 0-3 at 180 Days
Description
The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Another measure of efficacy is the mRS score, dichotomized to define good functional outcome as mRS 0-3 at 180 days.
Time Frame
180 days
Title
Number of Subjects Experiencing Serious Adverse Events
Description
Number of subjects experiencing Serious adverse events at any time from randomization through day 90
Time Frame
90 days
Title
Number of Subjects With Serious Adverse Events Within 7 Days
Description
Number of Subjects Experiencing Serious Adverse Events within 7 days of randomization
Time Frame
7 days
Other Pre-specified Outcome Measures:
Title
Changes of intracerebral hematoma volume
Description
Intracerebral hematoma volume (ml) is assessed by CT brain scan
Time Frame
0-7 days after enrollment.
Title
Changes of perihematomal edema volume
Description
Perihematomal edema volume (ml) is assessed by CT brain scan
Time Frame
0-7 days after enrollment.
Title
Ordinal Distribution of Scores on mRS at Day 90
Description
The overall ordinal distribution of scores on mRS at 90 days in all subjects of two groups will be determined.
Time Frame
90 days
Title
Ordinal Distribution of Scores on mRS at Day 180
Description
The overall ordinal distribution of scores on mRS at 180 days in all subjects of two groups will be determined.
Time Frame
180 days
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:
Age ≥ 18 and ≤ 80 years
The diagnosis of supratentorial ICH is confirmed by brain CT scan
Hematoma volume of 10 to 30 ml and Glasgow Coma Score (GCS)>8 at randomization.
National Institutes of Health Stroke Scale (NIHSS)≥6 and ≤20 points at randomization.
Randomization and starting treatment between 24 and 48 hours of symptom ictus.
Signed and dated informed consent is obtained.
Exclusion Criteria:
Planned surgical evacuation of ICH prior to administration of investigational intervention
ICH concomitant with subarachnoid hemorrhage or intraventricular hemorrhage
Suspected secondary ICH related to tumor, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis
Patients with a pre-existing neurological deficit (mRS>1) or psychiatric disease that would confound the neurological or functional evaluations.
Coagulopathy - defined as elevated aPTT or INR >1.3 upon presentation; concurrent use of direct thrombin inhibitors (such as dabigatran), direct factor Xa inhibitors (such as rivaroxaban or apixaban), or low-molecular-weight heparin
Severe renal disease (i.e., renal disorder requiring dialysis ) or eGFR <30ml/min/1.73m2
Severe liver disorder, or ALT >3 times or bilirubin >2 times upper limit of normal
Known severe hearing loss or cognitive impairment
Known pregnancy, or positive pregnancy test, or breastfeeding
Patients known or suspected of not being able to comply with the study protocol due to alcoholism, noncompliance or any other cause
Life expectancy of less than 90 days due to co-morbid conditions
Concurrent participation in another research protocol for investigation of another experimental therapy
Severe, sustained hypertension (Systolic blood pressure> 180 mmHg or diastolic blood pressure> 110 mmHg).
Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs.
Any condition which, in the judgement of the investigator, might increase the risk to the patient.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xunming Ji, MD, PhD
Phone
010-83199430
Email
jixm@ccmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Wenbo Zhao, MD, PhD
Phone
86-13120136877
Email
zhaowb@xwh.ccmu.edu.cn
Facility Information:
Facility Name
Xuanwu Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100053
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Beijing Red Cross Emergency Rescue Center
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Active, not recruiting
Facility Name
Beijing Renhe Hospital
City
Beijing
State/Province
Beijng
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Na Li, M.D.
Facility Name
Chengde Central Hospital
City
Chengde
State/Province
Hebei
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiangtao Zhang
Facility Name
The Six People's Hospital of Hengshui
City
Hengshui
State/Province
Hebei
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xinjing Gao
Facility Name
Nanshi Hospital of Nanyang
City
Nanyang
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rongyao Ma
Facility Name
Tongliao Municipal Hosptial
City
Tongliao
State/Province
Inner Mongolia Autonomous Region
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yaoming Xu, M.D.
Facility Name
The First People's Hospital of Changzhou
City
Changzhou
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Song Yang, M.D.
Facility Name
The Affiliated Hospital of Xuzhou Medical University
City
Xuzhou
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deqin Geng, MD
Facility Name
Tianjin Huanhu Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300350
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ming Wei, MD
Facility Name
Jiaxing Second Hospital
City
Jiaxing
State/Province
Zhejiang
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianguo Shen
Facility Name
Shaoxing People's Hospital
City
Shaoxing
State/Province
Zhejiang
ZIP/Postal Code
312000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xuebin Yu, MD
Facility Name
Zhuji People's Hospital of Zhejaing Province
City
Zhuji
State/Province
Zhejiang
Country
China
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33174815
Citation
Shoamanesh A, Patrice Lindsay M, Castellucci LA, Cayley A, Crowther M, de Wit K, English SW, Hoosein S, Huynh T, Kelly M, O'Kelly CJ, Teitelbaum J, Yip S, Dowlatshahi D, Smith EE, Foley N, Pikula A, Mountain A, Gubitz G, Gioia LC. Canadian stroke best practice recommendations: Management of Spontaneous Intracerebral Hemorrhage, 7th Edition Update 2020. Int J Stroke. 2021 Apr;16(3):321-341. doi: 10.1177/1747493020968424. Epub 2020 Nov 11.
Results Reference
background
PubMed Identifier
26022637
Citation
Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, Fung GL, Goldstein JN, Macdonald RL, Mitchell PH, Scott PA, Selim MH, Woo D; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015 Jul;46(7):2032-60. doi: 10.1161/STR.0000000000000069. Epub 2015 May 28.
Results Reference
background
PubMed Identifier
33739197
Citation
Zhao W, Jiang F, Li S, Liu G, Wu C, Wang Y, Ren C, Zhang J, Gu F, Zhang Q, Gao X, Gao Z, Song H, Ma Q, Ding Y, Ji X; RICH-1 Investigators. Safety and efficacy of remote ischemic conditioning for the treatment of intracerebral hemorrhage: A proof-of-concept randomized controlled trial. Int J Stroke. 2022 Apr;17(4):425-433. doi: 10.1177/17474930211006580. Epub 2021 Apr 7.
Results Reference
background
Learn more about this trial
Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage
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