Clinical trial NCT04657133: Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage
Official title: The Safety and Efficacy of Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage: A Multicenter, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Intracerebral Hemorrhage
Acute Stroke
Keywords: Therapy
Neuroprotection
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2020-12-08
Enrollment: 452
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days
timeFrame: 0-90 days.
Secondary outcomes:
measure: Proportion of Patients With mRS Score 0-3 at 90 Days
timeFrame: 90 days
measure: Proportion of Patients With mRS Score 0-2 at 180 Days
timeFrame: 180 days
measure: Proportion of Patients With mRS Score 0-3 at 180 Days
timeFrame: 180 days
measure: Number of Subjects Experiencing Serious Adverse Events
timeFrame: 90 days
measure: Number of Subjects With Serious Adverse Events Within 7 Days
timeFrame: 7 days
Other outcomes:
measure: Changes of intracerebral hematoma volume
timeFrame: 0-7 days after enrollment.
measure: Changes of perihematomal edema volume
timeFrame: 0-7 days after enrollment.
measure: Ordinal Distribution of Scores on mRS at Day 90
timeFrame: 90 days
measure: Ordinal Distribution of Scores on mRS at Day 180
timeFrame: 180 days
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Red Cross Emergency Rescue Center
state: Beijing
city: Beijing
country: China
facility: Beijing Renhe Hospital
state: Beijng
city: Chengde
country: China
facility: Chengde Central Hospital
state: Hebei
city: Hengshui
country: China
facility: The Six People's Hospital of Hengshui
state: Hebei
city: Nanyang
country: China
facility: Nanshi Hospital of Nanyang
state: Henan
city: Tongliao
country: China
facility: Tongliao Municipal Hosptial
state: Inner Mongolia Autonomous Region
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital
state: Tianjin
city: Jiaxing
country: China
facility: Jiaxing Second Hospital
state: Zhejiang
city: Shaoxing
country: China
facility: Shaoxing People's Hospital
state: Zhejiang
city: Zhuji
country: China
facility: Zhuji People's Hospital of Zhejaing Province
state: Zhejiang
Study officials:
References:
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.
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.
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.