Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage

Acute Stroke Clinical Trial

— RICH-2  

Official title:

The Safety and Efficacy of Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage: A Multicenter, Randomized, Controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04657133
• Other study ID #: RICH-2
• Status: Recruiting
• Phase: Phase 3
• Start date: April 22, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: July 2022
• Source: Capital Medical University
• Contact: Xunming Ji, MD, PhD
• Phone: 010-83199430
• Email: jixm[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 452
• Est. completion date: June 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age = 18 and = 80 years

2. The diagnosis of supratentorial ICH is confirmed by brain CT scan

3. Hematoma volume of 10 to 30 ml and Glasgow Coma Score (GCS)>8 at randomization.

4. National Institutes of Health Stroke Scale (NIHSS)=6 and =20 points at randomization.

5. Randomization and starting treatment between 24 and 48 hours of symptom ictus.

6. Signed and dated informed consent is obtained.

Exclusion Criteria:

1. Planned surgical evacuation of ICH prior to administration of investigational intervention

2. ICH concomitant with subarachnoid hemorrhage or intraventricular hemorrhage

3. Suspected secondary ICH related to tumor, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis

4. Patients with a pre-existing neurological deficit (mRS>1) or psychiatric disease that would confound the neurological or functional evaluations.

5. 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

6. Severe renal disease (i.e., renal disorder requiring dialysis ) or eGFR <30ml/min/1.73m2

7. Severe liver disorder, or ALT >3 times or bilirubin >2 times upper limit of normal

8. Known severe hearing loss or cognitive impairment

9. Known pregnancy, or positive pregnancy test, or breastfeeding

10. Patients known or suspected of not being able to comply with the study protocol due to alcoholism, noncompliance or any other cause

11. Life expectancy of less than 90 days due to co-morbid conditions

12. Concurrent participation in another research protocol for investigation of another experimental therapy

13. Severe, sustained hypertension (Systolic blood pressure> 180 mmHg or diastolic blood pressure> 110 mmHg).

14. Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs.

15. Any condition which, in the judgement of the investigator, might increase the risk to the patient.

Related Conditions & MeSH terms

• Acute Stroke
• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage
• Stroke

Intervention

Device:
• Remote ischemic conditioning
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.
• Sham remote ischemic conditioning
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.

Drug:
• Standard medication therapy
Standard medication therapy will be performed according to the national and international guidelines.

Locations

Country	Name	City	State
China	Beijing Red Cross Emergency Rescue Center	Beijing	Beijing
China	Beijing Renhe Hospital	Beijing	Beijng
China	Xuanwu Hospital, Capital Medical University	Beijing	Beijing
China	The First People's Hospital of Changzhou	Changzhou	Jiangsu
China	Chengde Central Hospital	Chengde	Hebei
China	The Six People's Hospital of Hengshui	Hengshui	Hebei
China	Jiaxing Second Hospital	Jiaxing	Zhejiang
China	Nanshi Hospital of Nanyang	Nanyang	Henan
China	Shaoxing People's Hospital	Shaoxing	Zhejiang
China	Tianjin Huanhu Hospital	Tianjin	Tianjin
China	Tongliao Municipal Hosptial	Tongliao	Inner Mongolia Autonomous Region
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Zhuji People's Hospital of Zhejaing Province	Zhuji	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Capital Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes of intracerebral hematoma volume	Intracerebral hematoma volume (ml) is assessed by CT brain scan	0-7 days after enrollment.
Other	Changes of perihematomal edema volume	Perihematomal edema volume (ml) is assessed by CT brain scan	0-7 days after enrollment.
Other	Ordinal Distribution of Scores on mRS at Day 90	The overall ordinal distribution of scores on mRS at 90 days in all subjects of two groups will be determined.	90 days
Other	Ordinal Distribution of Scores on mRS at Day 180	The overall ordinal distribution of scores on mRS at 180 days in all subjects of two groups will be determined.	180 days
Primary	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.	0-90 days.
Secondary	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.	90 days
Secondary	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.	180 days
Secondary	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.	180 days
Secondary	Number of Subjects Experiencing Serious Adverse Events	Number of subjects experiencing Serious adverse events at any time from randomization through day 90	90 days
Secondary	Number of Subjects With Serious Adverse Events Within 7 Days	Number of Subjects Experiencing Serious Adverse Events within 7 days of randomization	7 days