Safety and Effectiveness of Remote Ischemic Conditioning Combined With Intravenous Thrombolysis in Treating Acute Ischemic Stroke

Study Overview
=================
Brief Summary
-----------------
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
-----------------
In this study, cases of ischemic stroke who undergo intravenous thrombolysis within 4.5 hours from onset are included. The experimental group receive basic treatment and remote ischemic conditioning for 200mmHg, 2 times within 6 hours to 24 hours from thrombolysis. The control group receive basic treatment and remote ischemic conditioning control for 60mmHg, 2 times within 6 hours to 24 hours from thrombolysis . 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
-----------------
Safety and Effectiveness of Remote Ischemic Conditioning Combined With Intravenous Thrombolysis in Treating Acute Ischemic Stroke

Conditions
-----------------
Acute Ischemic Stroke

Intervention / Treatment
-----------------
* Device: remote ischemic conditioning
* Device: sham remote ischemic conditioning


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1) Age≥18 years, < 80 years, regardless of sex; 2) Patients with clinically definite diagnosis of acute ischemic stroke and undergo intravenous thrombolysis; 3) Baseline NIHSS >= 5, and <= 25; 4) Baseline GCS ≥8; 5) Signed and dated informed consent is obtained Exclusion Criteria: 1) Patients who undergo endovascular treatment; 2) mRS ≥ 2 before the onset of the disease; 3) Double upper limbs or lower limbs paralysis was found in this case; 4) Active bleeding of organs within 6 months of admission or current, including cerebral hemorrhage, subarachnoid hemorrhage, gastrointestinal hemorrhage, fundus hemorrhage and so on; 5) Other intracranial lesions, such as cerebrovascular malformation cerebral venous diseases, tumor and other diseases involving the brain; 6) Concurrent use of anticoagulation drugs including Warfarin, dabigatran, rivaroxaban; 7) Severe organ dysfunction or failure; 8) Patients suffering from severe hematological diseases or severe coagulation disorder dysfunction 9) Those who have a history of severe trauma or had major surgery within 6 months prior to admission; 10) Those who have a history of atrial fibrillation; 11) 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; 12) Pregnant or lactating women; 13) Previous remote ischemic conditioning therapy or similar treatment; 14) Patients with a life expectancy of less than 3 months or patients unable to complete the study for other reasons; 15) Severe hepatic and renal dysfunction; 16) Unwilling to be followed up or treated for poor compliance; 17) 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; 18) Other conditions that the researchers think are not suitable for the group.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RIC group<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 re-perfusion. Limb ischemia was induced by inflation of a blood pressure cuff to 200 mm Hg. RIC will be conducted twice within 6 to 24 hours from thrombolysis. Additionally,the patients will be treated with standard medical treatment according to Guidelines for diagnosis and treatment of acute ischemic stroke in China 2014. | Device: 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 re-perfusion. Limb ischemia was induced by inflation of a blood pressure cuff to 200 mm Hg.<br>|
| Placebo Comparator: control group<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 re-perfusion. Limb ischemia was induced by inflation of a blood pressure cuff to 60 mm Hg. RIC will be conducted twice twice within 6 to 24 hours from thrombolysis. Additionally,the patients will be treated with standard medical treatment according to Guidelines for diagnosis and treatment of acute ischemic stroke in China 2014 | Device: 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 re-perfusion. Limb ischemia was induced by inflation of a blood pressure cuff to 60 mm Hg.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events during hospitalization | All adverse events until day-7 or discharge (whichever is earlier) | 7 days | 
| Frequency of adverse events during follow-up | Severe adverse events through day-90 after the onset of acute ischemic stroke. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institute of Health stroke scale (NIHSS) at 7 days from onset or discharge | National Institute of Health stroke scale (NIHSS) at 7 days from onset or discharge. Ranged from 0 to 42, a low value represents a better outcome. | 7 days | 
| Proportion of patients with Modified Rankin Scale (mRS) Score 0-2 | Proportion of patients with Modified Rankin Scale (mRS) Score 0-2. Ranged from 0 to 6, a low value represents a better outcome. | 3 months |