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

Primary Purpose

Acute Stroke

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Remote ischemic conditioning
Endovascular treatment
Sponsored by
Capital Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional device feasibility trial for Acute Stroke focused on measuring Acute ischemic stroke, Endovascular treatment, Remote ischemic conditioning, Reperfusion therapy, Neuroprotection

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Xuanwu Hospital, Capital Medical University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RIC & ET

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of participants with any RIC-related adverse events.
For all participants, adverse events will be assessed by as assessed by CTCAE v4.0.

Secondary Outcome Measures

Change in cerebral artery blood flow velocity
Cerebral artery blood flow velocity is recorded continuously by Transcranial Doppler (TCD) during remote ischemic conditioning.
Change in vital signs
Vital signs are documented continuously during remote ischemic conditioning.
Change in intracranial pressure
Intracranial pressure is monitored by noninvasive intracranial pressure monitoring equipment during remote ischemic conditioning
Change in plasma biomarkers
Plasma biomarkers include biochemical biomarkers (e.g.,creatine kinase), blood routine test and coagulation function (e.g., PT, APTT, TT).
Final cerebral infarct volume.
The final infarct volume of cerebral infarct is evaluated by cranial noncontrast CT.
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.
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).
Symptomatic Intracerebral Hemorrhage.
Deterioration in NIHSS score of ≥4 points within 24 hours from treatment and evidence of hemorrhage in imaging scans.
Any adverse event.
Adverse events related or not related to remote ischemic conditioning will be documented.

Full Information

First Posted
June 26, 2017
Last Updated
December 20, 2017
Sponsor
Capital Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT03210051
Brief Title
Remote Ischemic Conditioning Paired With Endovascular Treatment for Acute Ischemic Stroke (REVISE-1)
Official Title
A Pilot Study Assessing the Safety and Feasibility of Remote Ischemic Conditioning Paired With Endovascular Treatment for Acute Ischemic Stroke
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
July 7, 2017 (Actual)
Primary Completion Date
September 17, 2017 (Actual)
Study Completion Date
December 20, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Capital Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Stroke
Keywords
Acute ischemic stroke, Endovascular treatment, Remote ischemic conditioning, Reperfusion therapy, Neuroprotection

7. Study Design

Primary Purpose
Device Feasibility
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RIC & ET
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Remote ischemic conditioning
Other Intervention Name(s)
RIC
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Endovascular treatment
Other Intervention Name(s)
ET
Intervention Description
Endovascular treatment include strategies that used to recanalize the occluded artery. Strategies often used include thrombectomy, intra-arterial thrombolysis, stenting and balloon angiography.
Primary Outcome Measure Information:
Title
Number of participants with any RIC-related adverse events.
Description
For all participants, adverse events will be assessed by as assessed by CTCAE v4.0.
Time Frame
0-90 days after endovascular treatment.
Secondary Outcome Measure Information:
Title
Change in cerebral artery blood flow velocity
Description
Cerebral artery blood flow velocity is recorded continuously by Transcranial Doppler (TCD) during remote ischemic conditioning.
Time Frame
0-7 days.
Title
Change in vital signs
Description
Vital signs are documented continuously during remote ischemic conditioning.
Time Frame
0-7 days.
Title
Change in intracranial pressure
Description
Intracranial pressure is monitored by noninvasive intracranial pressure monitoring equipment during remote ischemic conditioning
Time Frame
0-7 days.
Title
Change in plasma biomarkers
Description
Plasma biomarkers include biochemical biomarkers (e.g.,creatine kinase), blood routine test and coagulation function (e.g., PT, APTT, TT).
Time Frame
0-7 days.
Title
Final cerebral infarct volume.
Description
The final infarct volume of cerebral infarct is evaluated by cranial noncontrast CT.
Time Frame
5-9 days after endovascular treatment.
Title
Number of subjects completing all the designed RIC procedures.
Description
9 times (36 cycles) of RIC interventions are planned to be applied to each subject pre and post-endovascular treatment for 7 consecutive days.
Time Frame
0-7 days.
Title
The severity of global disability at 90 days, as assessed by modified Rankin scale (mRS).
Description
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).
Time Frame
0-90 days.
Title
Symptomatic Intracerebral Hemorrhage.
Description
Deterioration in NIHSS score of ≥4 points within 24 hours from treatment and evidence of hemorrhage in imaging scans.
Time Frame
0-90 days.
Title
Any adverse event.
Description
Adverse events related or not related to remote ischemic conditioning will be documented.
Time Frame
0-90 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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; No remarkable pre-stroke functional disability (mRS ≤ 1); Age ≥18 and ≤ 80; Patient treatable within six hours of symptom onset; Informed consent obtained from patient or acceptable patient's surrogate Exclusion Criteria: Identified hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 3.0; Baseline platelet count < 30*109/L; Baseline blood glucose of < 2.7mmol/L or >22.2mmol/L; Renal insufficiency with creatinine ≥ 265 umol/L; Severe, sustained hypertension (SBP > 185 mmHg or DBP > 110 mmHg); Woman of childbearing potential who is known to be pregnant or lactating; Subject participating in a study involving other drug or device trial study; Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations; Unlikely to be available for 90-day follow-up; Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs; Hypodensity on CT or restricted diffusion amounting to an ASPECTS score of <7 on noncontrast CT; CT or MRI evidence of hemorrhage; Significant mass effect with midline shift on CT or MRI scans; Subjects with artery occlusions in multiple vascular territories; Evidence of intracranial tumor.
Facility Information:
Facility Name
Xuanwu Hospital, Capital Medical University
City
Beijing
ZIP/Postal Code
100053
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
27766474
Citation
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.
Results Reference
background
PubMed Identifier
25868435
Citation
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.
Results Reference
background
PubMed Identifier
23035060
Citation
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.
Results Reference
background

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

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