Safety and Efficacy of Remote Ischemic Conditioning for Spontaneous Intracerebral Hemorrhage

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the efficacy and safety of remote ischemic conditioning in treating acute intracerebral hemorrhage.

Detailed Description
-----------------
Spontaneous intracerebral hemorrhage is a major cause of disability and mortality among different types of stroke, and few effective treatment options are available. Therefore, it is essential to develop new approaches to improve the prognosis of these patients. Recently, remote ischemic conditioning (RIC), a method that involves inducing multiple brief episodes of ischemia and reperfusion in the limbs, has been indicated to exert neuroprotective effects in experimental stroke. The underlying neuroprotective mechanism triggered by RIC induces gene expression, alters pathways, promotes neurogenesis and blood vessel development, reduces oxidative stress and neuronal apoptosis, and inhibits proinflammatory signals. Previously, several clinical trials have shown that single or repeated RIC treatments for cerebrovascular diseases are feasible and safe. Therefore, we hypothesize that RIC could improve functional outcome in patients with intracerebral hemorrhage. We design this prospective, multicenter, randomized controlled trial to evaluate the efficacy and safety of RIC in treating intracerebral hemorrhage.

Official Title
-----------------
Safety and Efficacy of Remote Ischemic Conditioning for Spontaneous Intracerebral Hemorrhage

Conditions
-----------------
Intracranial Hemorrhages

Intervention / Treatment
-----------------
* Device: Remote ischemic conditioning
* Device: Sham remote ischemic conditioning


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years. Supratentorial intracerebral hemorrhage confirmed by brain CT scan. No disability in the community before ICH (premorbid mRS≤ 1). NIHSS score ≥ 6 and GCS ≥ 8 upon presentation. Able to commence RIC treatment within 24 hours of stroke onset. Systolic blood pressure ≤ 180 mmHg before randomization. Signed and dated informed consent is obtained. Exclusion Criteria: Definite evidence of secondary ICH, such as structural abnormality, brain aneurysm, brain tumor, thrombolytic drug. Hematoma with a mid-line shift, cerebral herniation or isolate intraventricular hemorrhage. Already booked for surgical treatment. Life expectancy of less than 180 days due to comorbid conditions. Concurrent use of anticoagulation drugs including Warfarin, dabigatran, rivaroxaban or coagulopathy (defined as INR, APTT, and PT beyond the upper limit of normal range). Any soft tissue, orthopedic, or vascular injury, wounds or fractures in healthy upper limb which may pose a contraindication for application of RIC. Severe hepatic and renal dysfunction, or ALT/AST >3 times upper limit of normal, or serum creatinine >265umol/l. Known pregnancy or breastfeeding. Patients being enrolled or having been enrolled in other clinical trial within 3 months prior to this clinical trial. A high likelihood that the patient will not adhere to the study treatment and follow up regimen. Patients unsuitable for enrollment in the clinical trial according to investigators decision making.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RIC group<br>Remote ischemic conditioning (RIC) is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 200 mmHg. | Device: Remote ischemic conditioning<br>* Remote ischemic conditioning is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 200 mmHg.<br>|
| Placebo Comparator: Sham RIC group<br>Sham remote ischemic conditioning (Sham RIC) is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflation of a blood pressure cuff to 60 mm Hg. | Device: Sham remote ischemic conditioning<br>* Remote ischemic conditioning is induced by 4 cycles of 5 min of healthy upper limb ischemia followed by 5 min reperfusion. Limb ischemia was induced by inflations of a blood pressure cuff to 60 mmHg.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with Modified Rankin Scale (mRS) Score 0-2 at 180 days | Proportion of patients with Modified Rankin Scale (mRS) Score 0-2. Ranged from 0 to 6, a low value represents a better outcome. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with Modified Rankin Scale (mRS) Score 0-2 at 90 days | Proportion of patients with Modified Rankin Scale (mRS) Score 0-2. Ranged from 0 to 6, a low value represents a better outcome. | 90 days | 
| Ordinal shift of the full range of mRS scores at 90 and 180 days | Ranged from 0 to 6, a low value represents a better outcome. | 90 days, 180 days | 
| Hematoma growth at 24 hours | The growth in hematoma volume after the onset of intracerebral hemorrhage, which is assessed by Computed Tomography (CT) brain scan. | 24 hours | 
| National Institute of Health stroke scale (NIHSS) at 7 days | National Institute of Health stroke scale (NIHSS) ranged from 0 to 42, a low value represents a better outcome. | 7 days | 
| Adverse events occurring in the course of the study. | The safety endpoints will include all adverse events, severe adverse events and RIC related adverse events. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Intracranial Hemorrhage, remote ischemic conditioning