Safety and Efficacy of Remote Ischemic Conditioning Combined With Intravenous Thrombolysis for Acute Ischemic Stroke

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of remote ischemic conditioning combined with intravenous thrombolysis in treating acute ischemic stroke.

Detailed Description
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In this study, 558 cases of ischemic stroke who undergo intravenous thrombolysis within 4.5 hours from the onset are included in 13 centers in China according to the principle of random, and parallel control. The experimental group receive basic treatment and remote ischemic conditioning for 200mmHg, 2 times per day for 7 consecutive days. The control group receive basic treatment and remote ischemic conditioning control for 60mmHg, 2 times per day for 7 consecutive days. Two groups will be followed up for 90 days to evaluate the efficacy and safety of remote ischemic conditioning combined with intravenous thrombolysis in treating acute ischemic stroke.

Official Title
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Safety and Efficacy of Remote Ischemic Conditioning Combined With Intravenous Thrombolysis for Acute Ischemic Stroke: A Multicenter, Randomized, Parallel-controlled Clinical Trial

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Procedure: Remote ischemic conditioning
* Procedure: Sham remote ischemic conditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Age≥18 years, regardless of sex; 2) Patients with a clinically definite diagnosis of acute ischemic stroke and undergo intravenous thrombolysis with alteplase; 3) Baseline NIHSS >= 4, and <= 24; 4) Baseline mRS 0-1; 5) Signed and dated informed consent is obtained; Exclusion Criteria: 1) Patients who have the contraindication of intravenous thrombolysis with alteplase. 2) The patients who have the contraindication of remote ischemic conditioning treatment, such as severe soft tissue injury, fracture or vascular injury in the upper limb. Acute or subacute venous thrombosis, arterial occlusive disease, subclavian steal syndrome, etc. 3) Pregnant or lactating women. 4) Previous remote ischemic conditioning therapy or similar treatment; 5) Severe hepatic and renal dysfunction. 6) Patients with a life expectancy of less than 3 months or patients unable to complete the study for other reasons. 7) Unwilling to be followed up or treated for poor compliance. 8) He/She is participating in other clinical research or has participated in other clinical research or has participated in this study within 3 months prior to admission. 9) Other conditions that the researchers think are not suitable for the group.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: RIC+Standard medical treatment<br>RIC+Standard medical treatment 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 inflation of a blood pressure cuff to 200 mm Hg. RIC will be conducted twice daily for 7 consecutive days from thrombolysis. Additionally, the patients will be treated with standard medical treatment according to the Guidelines for diagnosis and treatment of acute ischemic stroke in China 2014. | Procedure: Remote ischemic conditioning<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 mm Hg.<br>|
| Placebo Comparator: Sham RIC+Standard medical treatment<br>Sham RIC+Standard medical treatment 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 inflation of a blood pressure cuff to 60 mm Hg. RIC will be conducted twice daily for 7 consecutive days from thrombolysis. Additionally, the patients will be treated with standard medical treatment according to the Guidelines for diagnosis and treatment of acute ischemic stroke in China 2014. | Procedure: Sham remote ischemic conditioning<br>* Sham 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 60 mm Hg.<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 0-1 | Proportion of patients with Modified Rankin Scale (mRS) Score 0-1. Ranged from 0 to 6, a low value represents a better outcome. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institute of Health stroke scale (NIHSS) at 24 hours, 7 days, 30±3 days, 90±3 days after IVT. | National Institute of Health stroke scale (NIHSS) at 24 hours, 7 days, 30±3 days, 90±3 days after IVT. Ranged from 0 to 42, a low value represents a better outcome. | 24 hours, 7 days, 30±3 days, 90±3 days | 
| Barthel Index (BI) at 24 hours, 7 days, 30±3 days, 90±3 days after IVT. | Barthel Index (BI) at 24 hours, 7 days, 30±3 days, 90±3 days after IVT. Ranged from 0 to 100, a high value represents a better outcome. | 24 hours, 7 days, 30±3 days, 90±3 days | 
| modified Rankin Scale (mRS) at 24 hours, 7 days, 30±3 days, 90±3 days after IVT. | modified Rankin Scale (mRS) at 24 hours, 7 days, 30±3 days, 90±3 days after IVT. Ranged from 0 to 6, a low value represents a better outcome. | 24 hours, 7 days, 30±3 days, 90±3 days | 
| Proportion of patients with modified Rankin Scale (mRS) Score 0-2, NIHSS score 0-1, Barthel Index (BI) ≥95 at 24 hours, 7 days, 30±3 days, 90±3 days after IVT. | Proportion of patients with modified Rankin Scale (mRS) Score 0-2, NIHSS score 0-1, Barthel Index (BI) ≥95 at 24 hours, 7 days, 30±3 days, 90±3 days after IVT. mRS: Ranged from 0 to 100, a high value represents a better outcome. NIHSS: Ranged from 0 to 42, a low value represents a better outcome. BI: Ranged from 0 to 100, a high value represents a better outcome. | 24 hours, 7 days, 30±3 days, 90±3 days | 
| Frequency of adverse events during follow-up | Severe adverse events through day-90 after the onset of acute ischemic stroke. | 90 days | 
| Frequency of Hemorrhagic transformation during hospitalization | Frequency of Hemorrhagic transformation during hospitalization | 7 days |