Remote Ischemic Conditioning Paired With Endovascular Treatment for Acute Ischemic Stroke (REVISE-1)

A Pilot Study Assessing the Safety and Feasibility of Remote Ischemic Conditioning Paired With Endovascular Treatment for Acute Ischemic Stroke

Currently, early reperfusion is considered as the most effective therapy for the treatment of acute ischemic stroke (AIS). Over the past 20 years, intravenous tissue plasminogen activator (IV tPA) has been demonstrated to be the only effective therapy for AIS. More recently, several large randomized clinical trials have concluded the superiority of endovascular mechanical thrombectomy for AIS. Furthermore, with the development of materials and techniques, the occluded artery can be recanalized with high percentage (60%-90%), and the rate of recanalization is still being improved. A great number of AIS patients are now eligible for revascularization therapy and there should be a good prognosis of AIS after recanalizing the occluded artery using mechanical thrombectomy. However, things are never as simple as wished to be. The rate of patients with functional independence is less than 50% and over 15% patients died at 3 months post thrombectomy. The discrepancy between the functional outcome and recanalization rates encourage researchers to explore strategies that further improving the functional outcome of AIS patients.

Remote ischemic conditioning has been demonstrated to reduce cerebral infarct size in mouse model of focal cerebral ischemia. And clinical researches demonstrated the protective effects of remote ischemic conditioning in AIS patient treated with IV tPA,. However, whether remote ischemic conditioning is safe and effective in protecting patients with large-vessel ischemic stroke and undergoing endovascular treatment is still unknown.

Study Overview

• Status: Completed
• Conditions: Acute Stroke
• Intervention / Treatment: Device: Remote ischemic conditioning; Procedure: Endovascular treatment

Detailed Description

In the present study, the investigators will assess the safety and feasibility of remote ischemic condition paired with endovascular treatment for AIS. A single arm of AIS patients treated with endovascular therapy will be recruited, and remote ischemic conditioning will be applied prior to reperfusion therapy and in combination with post reperfusion therapy.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100053
    • Xuanwu Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acute ischemic stroke where patient is ineligible for intravenous thrombolytic treatment or the treatment is contraindicated, or where patient has received intravenous thrombolytic therapy without recanalization;
2. No remarkable pre-stroke functional disability (mRS ≤ 1);
3. Age ≥18 and ≤ 80;
4. Patient treatable within six hours of symptom onset;
5. Informed consent obtained from patient or acceptable patient's surrogate

Exclusion Criteria:

1. Identified hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 3.0;
2. Baseline platelet count < 30*109/L;
3. Baseline blood glucose of < 2.7mmol/L or >22.2mmol/L;
4. Renal insufficiency with creatinine ≥ 265 umol/L;
5. Severe, sustained hypertension (SBP > 185 mmHg or DBP > 110 mmHg);
6. Woman of childbearing potential who is known to be pregnant or lactating;
7. Subject participating in a study involving other drug or device trial study;
8. Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations;
9. Unlikely to be available for 90-day follow-up;
10. Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs;
11. Hypodensity on CT or restricted diffusion amounting to an ASPECTS score of <7 on noncontrast CT;
12. CT or MRI evidence of hemorrhage;
13. Significant mass effect with midline shift on CT or MRI scans;
14. Subjects with artery occlusions in multiple vascular territories;
15. Evidence of intracranial tumor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: RIC & ET; Remote ischemic conditioning paired with endovascular treatment. RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on bilateral arms and inflated to 200 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times. Endovascular treatment of acute ischemic stroke is performed by experienced neuroradiologist according to the latest guideline from American Heart Association and American Stroke Association. It includes thrombectomy, intra-arterial thrombolysis, thrombus aspiration, stenting and balloon angioplasty.

Device: Remote ischemic conditioning; RIC is a physical strategy performed by an electric autocontrol device with cuffs placed on bilateral arms and inflated to 200 mmHg for 5-min followed by deflation for 5-min, the procedures is performed repeatedly for 5 times.; Other Names: RIC; Procedure: Endovascular treatment; Endovascular treatment include strategies that used to recanalize the occluded artery. Strategies often used include thrombectomy, intra-arterial thrombolysis, stenting and balloon angiography.; Other Names: ET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with any RIC-related adverse events.	For all participants, adverse events will be assessed by as assessed by CTCAE v4.0.	0-90 days after endovascular treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The severity of global disability at 90 days, as assessed by modified Rankin scale (mRS).	The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death).	0-90 days.
Change in cerebral artery blood flow velocity	Cerebral artery blood flow velocity is recorded continuously by Transcranial Doppler (TCD) during remote ischemic conditioning.	0-7 days.
Change in vital signs	Vital signs are documented continuously during remote ischemic conditioning.	0-7 days.
Change in intracranial pressure	Intracranial pressure is monitored by noninvasive intracranial pressure monitoring equipment during remote ischemic conditioning	0-7 days.
Change in plasma biomarkers	Plasma biomarkers include biochemical biomarkers (e.g.,creatine kinase), blood routine test and coagulation function (e.g., PT, APTT, TT).	0-7 days.
Final cerebral infarct volume.	The final infarct volume of cerebral infarct is evaluated by cranial noncontrast CT.	5-9 days after endovascular treatment.
Number of subjects completing all the designed RIC procedures.	9 times (36 cycles) of RIC interventions are planned to be applied to each subject pre and post-endovascular treatment for 7 consecutive days.	0-7 days.
Symptomatic Intracerebral Hemorrhage.	Deterioration in NIHSS score of ≥4 points within 24 hours from treatment and evidence of hemorrhage in imaging scans.	0-90 days.
Any adverse event.	Adverse events related or not related to remote ischemic conditioning will be documented.	0-90 days.

Collaborators and Investigators

• Sponsor: Capital Medical University

Publications and helpful links

General Publications

• Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, Li G, Ren C, Luo Y, Ling F, Jia J, Hua Y, Wang X, Ding Y, Lo EH, Ji X. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012 Oct 30;79(18):1853-61. doi: 10.1212/WNL.0b013e318271f76a. Epub 2012 Oct 3.
• Hausenloy DJ, Barrabes JA, Botker HE, Davidson SM, Di Lisa F, Downey J, Engstrom T, Ferdinandy P, Carbrera-Fuentes HA, Heusch G, Ibanez B, Iliodromitis EK, Inserte J, Jennings R, Kalia N, Kharbanda R, Lecour S, Marber M, Miura T, Ovize M, Perez-Pinzon MA, Piper HM, Przyklenk K, Schmidt MR, Redington A, Ruiz-Meana M, Vilahur G, Vinten-Johansen J, Yellon DM, Garcia-Dorado D. Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery. Basic Res Cardiol. 2016 Nov;111(6):70. doi: 10.1007/s00395-016-0588-8. Epub 2016 Oct 20.
• Ren C, Wang P, Wang B, Li N, Li W, Zhang C, Jin K, Ji X. Limb remote ischemic per-conditioning in combination with post-conditioning reduces brain damage and promotes neuroglobin expression in the rat brain after ischemic stroke. Restor Neurol Neurosci. 2015;33(3):369-79. doi: 10.3233/RNN-140413.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2017
• Primary Completion (Actual): September 17, 2017
• Study Completion (Actual): December 20, 2017

Study Registration Dates

• First Submitted: June 26, 2017
• First Submitted That Met QC Criteria: July 4, 2017
• First Posted (Actual): July 6, 2017

Study Record Updates

• Last Update Posted (Actual): December 22, 2017
• Last Update Submitted That Met QC Criteria: December 20, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Neuroprotection; Acute ischemic stroke; Endovascular treatment; Remote ischemic conditioning; Reperfusion therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia
• Other Study ID Numbers: RIC-AIS-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No