Back to resultsNeuroprotective Effect of Remote Ischemic Conditioning in Ischemic Stroke Treated With Mechanical Thrombectomy (PROTECT I)
Primary Purpose
Stroke, Ischemic
Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Remote ischemic conditioning
Patients with a sham procedure of remote ischemic conditioning
Sponsored by
About this trial
This is an interventional treatment trial for Stroke, Ischemic focused on measuring Ischemic stroke, Mechanical Thrombectomy, Ischemia/Reperfusion, Remote Ischemic Conditioning, Magnetic Resonance Imaging
Eligibility Criteria
Inclusion Criteria:
- Age at least 18 years old,
- Carotid ischemic stroke related to a full occlusion of the middle cerebral artery (occlusion of middle 1 (M1) and/or proximal middle 2 (M2) identified as candidate for endovascular intervention according to local criteria,
- Brain Magnetic Resonance Imaging (MRI) performed within 6 hours from symptoms onset,
- Acute stroke MRI including at least diffusion weighted imaging (DWI), fluid attenuated inversion recovery (FLAIR), intracranial vessel imaging with Magnetic Resonance Angiography (MRA) and perfusion weighted imaging (PWI),
- Modified Rankin Score (mRS) score less than or equal to 1 before ischemic stroke,
- Obtaining a written informed consent of the patient or a next of kin, or emergency inclusion process.
Non inclusion Criteria:
- Previous ischemic stroke or transient ischemic attack (TIA) in the previous 3 months,
- Contraindications to iodinated contrast agents,
- Sickle cell disease known (risk of vaso-occlusive crisis),
- Life expectancy less than 90 days,
- Pregnant or women of childbearing age who were not using contraception (oral diagnosis),
- Patient without health coverage,
- Patient under legal protection.
- Any contraindication to Magnetic Resonance Imaging (MRI) (example cardiac pacemaker),
- Intracranial bleeding,
- Intracranial expansive process.
Exclusion Criteria:
- Recanalization of M1 or proximal M2 segment at the time of thrombectomy
Sites / Locations
- Service De Neurologie Vasculaire - Hôpital Neurologique Pierre Wertheimer (GHE)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Remote Ischemic Conditioning (RIC) positive
Control group
Arm Description
Patients with remote ischemic conditioning
The control group will receive a sham procedure (same procedure than Remote Ischemic Conditioning (RIC) with brachial cuff inflation to 30 millimeters (mm) of mercury (Hg) during 40 minutes).
Outcomes
Primary Outcome Measures
Final volume of cerebral infarction measured by Magnetic Resonance Imaging (MRI) at Day 1 after thrombectomy
Measurement of the final volume of cerebral infarction on Fluid Attenuated Inversion Recovery (FLAIR) sequence by a blinding imaging reading committee.
Secondary Outcome Measures
Change in Neurological prognosis
Functional neurological prognosis assessed by: 1/ National Institutes of Health Stroke Scale (NIHSS) score on day 7 (NIHSS score for each ability is a number between 0 and 4 with 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. The higher the score, the more impaired neurologically a stroke patient is) 2/ Modified Rankin Score (MRS) score at 90 days (score from 0 to 6 with 0 being normal functioning and 6 being death, the higher the score the more impaired neurologically a stroke patient is) and 3/ Incidence of early neurological worsening (Difference in NIHSS score between inclusion and day 1 > 4 points).
Change in growth of the supposed irreversible lesion measured by Magnetic Resonance Imaging (MRI) from admission to day 1.
It will be expressed as a percentage of the size of the hypoperfused area measured on the admission Magnetic Resonance Imaging (MRI).
Arterial reperfusion measured by the Thrombolysis in Cerebral Infarction (TICI) score at the end of the thrombectomy procedure.
The Thrombolysis in Cerebral Infarction (TICI) score is a tool for determining the response of thrombolytic therapy for ischemic stroke and is defined as follows: 0=no perfusion; 1= penetration, but no distal branch filling; 2a= perfusion with incomplete (<50%) distal branch filling; 2b=perfusion with incomplete (>50%) distal branch filling; and 3=full perfusion with filling of all distal branches. A score of 0 being the least favorable outcome for the patient (no perfusion) and a maximum score of 3 being the most favorable outcome for the patient (full perfusion).
Arterial reperfusion measured at Day 1 by Magnetic Resonance Imaging (MRI).
Arterial reperfusion according to the Arterial Occlusive Lesion (AOL) score. This score is related to recanalization of the primary arterial occlusive lesion on a scale of 0 to 3 : 0 is no recanalization of the primary occlusive lesion; 1 is incomplete or partial recanalization of the primary occlusive lesion with no distal flow; 2 is incomplete or partial recanalization of the primary lesion with any distal flow; and 3 is complete recanalization of the primary occlusive lesion with any distal flow. The most favorable outcome for the patient is a score of 3 while a score of 0 is the least favorable patient outcome.
Impact on collateral circulation assessed by the Higashida score.
Higashida score offers a non-invasive collateral vessel and tissue perfusion assessment of ischemic tissue. This grading system subdivides the collateral flow into five grades, from grade 0 (no collaterals visible on the ischemic side) to grade 5 (complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion). A grade of 3-5 is considered good collateral formation whereas a grade of 0-2 is considered poor collateral formation after a stroke and is less favorable to the patient's outcome.
Incidence of hemorrhagic transformation at day 1 measured by routine Magnetic Resonance Imaging (MRI)
European Cooperative Acute Stroke Study (ECASS) classification of potential haemorrhagic transformation which divides hemorrhagic transformation into four subtypes: 1) hemorrhagic infarction type 1 (HI1) such as petechial hemorrhages at the infarct margins; 2) hemorrhagic infarction type 2 (HI2) such as petechial hemorrhages throughout the infarct and no mass-effect attributable to the hemorrhages; 3) parenchymal hematoma type 1 (PH1) such as less than or equal to 30% of the infarcted area minor mass effect attributable to the hematoma and 4) parenchymal hematoma type 2 (PH2) such as greater than 30% of infarct zone substantial mass effect attributable to the hematoma. The most favorable patient outcome being the first classification hemorrhagic infarction type 1 (HI1) and the least favorable patient outcome being the fourth classification parenchymal hematoma type 2 (PH2).
Complications related to the endovascular procedure
Complications such as: embolism in an another initially not involved vascular territory, dissection, severe vasospasm that needs an intra-arterial treatment, vascular perforation
Responder analysis to thrombectomy relating Modified Rankin score (mRS) 90 days after stroke to baseline National Institutes of Health Stroke Scale (NIHSS) score.
NIHSS score for each ability is a number between 0 and 4 with 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. The higher the score, the more impaired a stroke patient is. MRS score from 0 to 6 with 0 being normal functioning and 6 being death, the higher the score the more impaired a stroke patient is. For this study a positive response is defined by : a NIHSS <7 at admission and a MRS = 0 at Day 90 ; a NIHSS between 8 and 14 at admission and a MRS = 0 or 1 at Day 90 ; a NIHSS >14 at admission and a MRS = 0 to 2 at Day 90.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03915782
Brief Title
Neuroprotective Effect of Remote Ischemic Conditioning in Ischemic Stroke Treated With Mechanical Thrombectomy
Acronym
PROTECT I
Official Title
NeuroPRotective Effect of remOte Ischemic condiTioning in Ischemic strokE Treated With meChanical Thrombectomy (PROTECT-I Study)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 20, 2020 (Actual)
Primary Completion Date
June 20, 2022 (Anticipated)
Study Completion Date
June 20, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
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
The benefit of mechanical thrombectomy in the treatment of ischemic stroke has been demonstrated in several multicenter randomized trials. However, it leads to a sudden reperfusion of the brain parenchyma associated to an extension of the infarct volume. Evidence has indicated that remote ischemic conditioning (RIC) reduces final infarct size in animal stroke models. The main objective of the present study is to determine whether remote ischemic conditioning can limit the final infarct volume after recanalization of the occluded cerebral artery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Ischemic
Keywords
Ischemic stroke, Mechanical Thrombectomy, Ischemia/Reperfusion, Remote Ischemic Conditioning, Magnetic Resonance Imaging
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
126 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Remote Ischemic Conditioning (RIC) positive
Arm Type
Experimental
Arm Description
Patients with remote ischemic conditioning
Arm Title
Control group
Arm Type
Sham Comparator
Arm Description
The control group will receive a sham procedure (same procedure than Remote Ischemic Conditioning (RIC) with brachial cuff inflation to 30 millimeters (mm) of mercury (Hg) during 40 minutes).
Intervention Type
Device
Intervention Name(s)
Remote ischemic conditioning
Intervention Description
Remote ischemic conditioning (RIC): Four cycles of [5 minutes of brachial cuff inflation at 200 millimeters (mm) of mercury (Hg) followed by 5 minutes of cuff deflation] started as soon as possible after Magnetic Resonance Imaging (MRI).
Intervention Type
Device
Intervention Name(s)
Patients with a sham procedure of remote ischemic conditioning
Intervention Description
Sham procedure: Four cycles of [5 minutes of brachial cuff inflation at 30 millimeters (mm) of mercury (Hg) followed by 5 minutes of cuff deflation] started as soon as possible after Magnetic Resonance Imaging (MRI).
Primary Outcome Measure Information:
Title
Final volume of cerebral infarction measured by Magnetic Resonance Imaging (MRI) at Day 1 after thrombectomy
Description
Measurement of the final volume of cerebral infarction on Fluid Attenuated Inversion Recovery (FLAIR) sequence by a blinding imaging reading committee.
Time Frame
Day 1 after thrombectomy
Secondary Outcome Measure Information:
Title
Change in Neurological prognosis
Description
Functional neurological prognosis assessed by: 1/ National Institutes of Health Stroke Scale (NIHSS) score on day 7 (NIHSS score for each ability is a number between 0 and 4 with 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. The higher the score, the more impaired neurologically a stroke patient is) 2/ Modified Rankin Score (MRS) score at 90 days (score from 0 to 6 with 0 being normal functioning and 6 being death, the higher the score the more impaired neurologically a stroke patient is) and 3/ Incidence of early neurological worsening (Difference in NIHSS score between inclusion and day 1 > 4 points).
Time Frame
1/ National Institutes of Health Stroke Scale (NIHSS) score will be evaluated at day 7; 2/ Modified Rankin Score (mRS) will be evaluated at day 90 and 3/ Incidence of early neurological worsening will be evaluated at inclusion and up to day 1.
Title
Change in growth of the supposed irreversible lesion measured by Magnetic Resonance Imaging (MRI) from admission to day 1.
Description
It will be expressed as a percentage of the size of the hypoperfused area measured on the admission Magnetic Resonance Imaging (MRI).
Time Frame
Magnetic Resonance Imaging (MRI) will be performed at inclusion (Day 0) and on day 1.
Title
Arterial reperfusion measured by the Thrombolysis in Cerebral Infarction (TICI) score at the end of the thrombectomy procedure.
Description
The Thrombolysis in Cerebral Infarction (TICI) score is a tool for determining the response of thrombolytic therapy for ischemic stroke and is defined as follows: 0=no perfusion; 1= penetration, but no distal branch filling; 2a= perfusion with incomplete (<50%) distal branch filling; 2b=perfusion with incomplete (>50%) distal branch filling; and 3=full perfusion with filling of all distal branches. A score of 0 being the least favorable outcome for the patient (no perfusion) and a maximum score of 3 being the most favorable outcome for the patient (full perfusion).
Time Frame
Day 1 of thrombectomy
Title
Arterial reperfusion measured at Day 1 by Magnetic Resonance Imaging (MRI).
Description
Arterial reperfusion according to the Arterial Occlusive Lesion (AOL) score. This score is related to recanalization of the primary arterial occlusive lesion on a scale of 0 to 3 : 0 is no recanalization of the primary occlusive lesion; 1 is incomplete or partial recanalization of the primary occlusive lesion with no distal flow; 2 is incomplete or partial recanalization of the primary lesion with any distal flow; and 3 is complete recanalization of the primary occlusive lesion with any distal flow. The most favorable outcome for the patient is a score of 3 while a score of 0 is the least favorable patient outcome.
Time Frame
Day 1
Title
Impact on collateral circulation assessed by the Higashida score.
Description
Higashida score offers a non-invasive collateral vessel and tissue perfusion assessment of ischemic tissue. This grading system subdivides the collateral flow into five grades, from grade 0 (no collaterals visible on the ischemic side) to grade 5 (complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion). A grade of 3-5 is considered good collateral formation whereas a grade of 0-2 is considered poor collateral formation after a stroke and is less favorable to the patient's outcome.
Time Frame
Day 1
Title
Incidence of hemorrhagic transformation at day 1 measured by routine Magnetic Resonance Imaging (MRI)
Description
European Cooperative Acute Stroke Study (ECASS) classification of potential haemorrhagic transformation which divides hemorrhagic transformation into four subtypes: 1) hemorrhagic infarction type 1 (HI1) such as petechial hemorrhages at the infarct margins; 2) hemorrhagic infarction type 2 (HI2) such as petechial hemorrhages throughout the infarct and no mass-effect attributable to the hemorrhages; 3) parenchymal hematoma type 1 (PH1) such as less than or equal to 30% of the infarcted area minor mass effect attributable to the hematoma and 4) parenchymal hematoma type 2 (PH2) such as greater than 30% of infarct zone substantial mass effect attributable to the hematoma. The most favorable patient outcome being the first classification hemorrhagic infarction type 1 (HI1) and the least favorable patient outcome being the fourth classification parenchymal hematoma type 2 (PH2).
Time Frame
Day 1
Title
Complications related to the endovascular procedure
Description
Complications such as: embolism in an another initially not involved vascular territory, dissection, severe vasospasm that needs an intra-arterial treatment, vascular perforation
Time Frame
Day 1
Title
Responder analysis to thrombectomy relating Modified Rankin score (mRS) 90 days after stroke to baseline National Institutes of Health Stroke Scale (NIHSS) score.
Description
NIHSS score for each ability is a number between 0 and 4 with 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. The higher the score, the more impaired a stroke patient is. MRS score from 0 to 6 with 0 being normal functioning and 6 being death, the higher the score the more impaired a stroke patient is. For this study a positive response is defined by : a NIHSS <7 at admission and a MRS = 0 at Day 90 ; a NIHSS between 8 and 14 at admission and a MRS = 0 or 1 at Day 90 ; a NIHSS >14 at admission and a MRS = 0 to 2 at Day 90.
Time Frame
Day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age at least 18 years old,
Carotid ischemic stroke related to a full occlusion of the middle cerebral artery (occlusion of middle 1 (M1) and/or proximal middle 2 (M2) identified as candidate for endovascular intervention according to local criteria,
Brain Magnetic Resonance Imaging (MRI) performed within 6 hours from symptoms onset,
Acute stroke MRI including at least diffusion weighted imaging (DWI), fluid attenuated inversion recovery (FLAIR), intracranial vessel imaging with Magnetic Resonance Angiography (MRA) and perfusion weighted imaging (PWI),
Modified Rankin Score (mRS) score less than or equal to 1 before ischemic stroke,
Obtaining a written informed consent of the patient or a next of kin, or emergency inclusion process.
Non inclusion Criteria:
Previous ischemic stroke or transient ischemic attack (TIA) in the previous 3 months,
Contraindications to iodinated contrast agents,
Sickle cell disease known (risk of vaso-occlusive crisis),
Life expectancy less than 90 days,
Pregnant or women of childbearing age who were not using contraception (oral diagnosis),
Patient without health coverage,
Patient under legal protection.
Any contraindication to Magnetic Resonance Imaging (MRI) (example cardiac pacemaker),
Intracranial bleeding,
Intracranial expansive process.
Exclusion Criteria:
Recanalization of M1 or proximal M2 segment at the time of thrombectomy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laura MECHTOUFF, MD
Phone
4 7 35 78 07
Ext
+33
Email
laura.mechtouff@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Marielle BUISSON
Phone
4 27 85 66 90
Ext
+33
Email
marielle.buisson01@chu-lyon.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laura MECHTOUFF, MD
Organizational Affiliation
Hospices Civils de Lyon, Hopital Pierre Wertheimer
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service De Neurologie Vasculaire - Hôpital Neurologique Pierre Wertheimer (GHE)
City
Bron
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura MECHTOUFF, Dr
Phone
04 27 85 67 47
Ext
+33
Email
laura.mechtouff@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Marielle BUISSON
Phone
04 27 85 66 90
Ext
+33
Email
marielle.buisson01@chu-lyon.fr
12. IPD Sharing Statement
Learn more about this trial
Neuroprotective Effect of Remote Ischemic Conditioning in Ischemic Stroke Treated With Mechanical Thrombectomy
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