Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage

Study Overview
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Brief Summary
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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.

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

Conditions
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Intracerebral Hemorrhage, Acute Stroke

Intervention / Treatment
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* Device: Remote ischemic conditioning
* Device: Sham remote ischemic conditioning
* Drug: Standard medication therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Subjects in the intervention group will receive remote ischemic conditioning and standard background medical treatment. | Device: Remote ischemic conditioning<br>* 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.<br>* Other names: RIC;Drug: Standard medication therapy<br>* Standard medication therapy will be performed according to the national and international guidelines.<br>|
| Placebo Comparator: Sham group<br>Subjects in the placebo group will receive sham remote ischemic conditioning and standard background medical treatment alone. | Device: Sham remote ischemic conditioning<br>* 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.<br>* Other names: Sham RIC;Drug: Standard medication therapy<br>* Standard medication therapy will be performed according to the national and international guidelines.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Number of Subjects Experiencing Serious Adverse Events | Number of subjects experiencing Serious adverse events at any time from randomization through day 90 | 90 days | 
| Number of Subjects With Serious Adverse Events Within 7 Days | Number of Subjects Experiencing Serious Adverse Events within 7 days of randomization | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Therapy, Neuroprotection