Analysis of Revascularization in Ischemic Stroke With EmboTrap (ARISEII)

• ClinicalTrials.gov Identifier: NCT02488915
• Recruitment Status: Completed
• First Posted: July 2, 2015
• Results First Posted: July 13, 2018
• Last Update Posted: July 13, 2018
• Sponsor: Neuravi Inc.
• Information provided by (Responsible Party): Neuravi Inc.

Tracking Information

• First Submitted Date: June 30, 2015
• First Posted Date: July 2, 2015
• Results First Submitted Date: May 17, 2018
• Results First Posted Date: July 13, 2018
• Last Update Posted Date: July 13, 2018
• Actual Study Start Date: November 2015
• Actual Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 13, 2018)

• Successful Revascularization Measured Using Modified Thrombolysis in Cerebrovascular Infarction (mTICI Inclusive of the 2c Rating) [ Time Frame: Post-treatment ]
  Successful achievement of the endpoint is defined as achieving an mTICI score of 2b or greater in the target vessel following 3 or less passes of the EmboTrap device. Patients treated with rescue prior to completion of three passes with EmboTrap were treated as failures to meet the primary revascularization endpoint. (Post measurement of the primary endpoint some patients subsequently received additional treatment.) - mTICI is a 6-point grading system for determining the response of thrombolytic therapy for ischaemic stroke: mTICI 0 = No perfusion mTICI 1 = Penetration but not perfusion mTICI 2a = Some perfusion with distal branch filling of <50% of territory visualized mTICI 2b = Substantial perfusion with distal branch filling of ≥50% of territory visualized mTICI 2c = Near-complete perfusion mTICI 3 = Complete perfusion
• Occurrence of Symptomatic Intracerebral Hemorrhage (sICH) Within 24 Hours Post-procedure and Any Other Serious Adverse Device Effects (SADE) [ Time Frame: 24(-8/+12 hrs) hours post-procedure and 90(±14) days Post Procedure ]
  The primary safety endpoint will be measured as the occurrence of Symptomatic Intracerebral hemorrhage (sICH) within 24 hours (-8/+12 hrs) post-procedure, together with any other Serious Adverse Device Effects (excluding those already counted in sICH). sICH was assessed using the Heidelberg Bleeding Classification, i.e. any intracerebral hemorrhage associated with an increase of ≥4 points in the NIHSS scale or an increase of ≥2 points of a NIHSS subcategory or that leads to major medical intervention. SADE was categorized as any serious adverse event that was deemed to be caused by the study device.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: June 13, 2018)

• Good Clinical Outcome as Defined by Modified Rankin Scale (mRS) Score ≤2 [ Time Frame: 90(±14) days Post Procedure ]
  Good Clinical Outcome is defined as achieving an mRS score of ≤2 at 90 days post procedure. - mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. mRS scores range from 0 to 6: mRS 0 = No symptoms. mRS 1 = No significant disability. mRS 2 = Slight disability. mRS 3 = Moderate disability. mRS 4 = Moderately severe disability. mRS 5 = Severe disability. mRS 6 = Dead.
• Procedure Time [ Time Frame: Post-treatment ]
  The time from groin puncture to achievement of mTICI ≥2b, or if not obtained, to the final angiogram. - mTICI is a 6-point grading system for determining the response of thrombolytic therapy for ischaemic stroke: mTICI 0 = No perfusion mTICI 1 = Penetration but not perfusion mTICI 2a = Some perfusion with distal branch filling of <50% of territory visualized mTICI 2b = Substantial perfusion with distal branch filling of ≥50% of territory visualized mTICI 2c = Near-complete perfusion mTICI 3 = Complete perfusion
• All Procedure-related Mortality [ Time Frame: Day 7 post-procedure ]
  Any death that is deemed to have been caused by the study procedure.
• All-cause Mortality [ Time Frame: 90(±14) days Post Procedure ]
  Any death that occurs within 90(±14) days post-procedure.
• Occurrence of Serious Adverse Device Effects (SADE) [ Time Frame: 90(±14) days Post Procedure ]
  SADE was categorized as any serious adverse event that was deemed to be caused by the study device.
• Occurrence of Procedure Related Serious Adverse Events (PRSAE) [ Time Frame: 90(±14) days Post Procedure ]
  PRSAE was categorized as any serious adverse event that was deemed to be caused by the study procedure.
• Occurrence of Symptomatic Intracerebral Hemorrhage (sICH) [ Time Frame: 24(-8/+12) hours post-procedure ]
  sICH was assessed using the Heidelberg Bleeding Classification, i.e. any intracerebral hemorrhage associated with an increase of ≥4 points in the NIHSS scale or an increase of ≥2 points of a NIHSS subcategory or that leads to major medical intervention.
• Occurrence of Neurological Deterioration [ Time Frame: 24(-8/+12) hours post-procedure ]
  An increase of 4 points or more on the National Institutes of Health Stroke Scale (NIHSS) at 24 hours (-8/+12 hrs) post-procedure. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. NIHSS scores range from 0 - 42. A score of 0 indicates no stroke symptoms. Higher scores indicate incremental levels of neurological impairment.
• Proportion of Subjects With Evidence of Infarction of a Previously Uninvolved Vascular Territory [ Time Frame: 24(-8/+12) hours post-procedure ]
  Infarction (i.e. brain tissue death) of a previously uninvolved vascular territory (i.e. region of the brain) is evaluated from 24-hour imaging (Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)).
• Time to Treat [ Time Frame: Post-treatment ]
  The time from first baseline angiogram to achievement of mTICI ≥2b, or if not obtained, to the final angiogram. - mTICI is a 6-point grading system for determining the response of thrombolytic therapy for ischaemic stroke: mTICI 0 = No perfusion mTICI 1 = Penetration but not perfusion mTICI 2a = Some perfusion with distal branch filling of <50% of territory visualized mTICI 2b = Substantial perfusion with distal branch filling of ≥50% of territory visualized mTICI 2c = Near-complete perfusion mTICI 3 = Complete perfusion

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Analysis of Revascularization in Ischemic Stroke With EmboTrap
• Official Title: ARISE II (Analysis of Revascularization in Ischemic Stroke With EmboTrap) Study
• Brief Summary: The study objective is to examine the recanalization efficacy of the EmboTrap device and its associated performance characteristics and to record associated clinical outcomes in a manner that facilitates relevant comparison of outputs with that of devices approved in the U.S. for clearing Large Vessel Occlusions.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Stroke
• Ischemia

Intervention

Device: EmboTrap® Revascularization Device

Other Name: EmboTrap II

Study Arms

Experimental: EmboTrap® Revascularization Device

Mechanical Thrombectomy with EmboTrap

Intervention: Device: EmboTrap® Revascularization Device

Publications *

• Yoo AJ, Soomro J, Andersson T, Saver JL, Ribo M, Bozorgchami H, Dabus G, Liebeskind DS, Jadhav A, Mattle H, Zaidat OO. Benchmarking the Extent and Speed of Reperfusion: First Pass TICI 2c-3 Is a Preferred Endovascular Reperfusion Endpoint. Front Neurol. 2021 May 11;12:669934. doi: 10.3389/fneur.2021.669934. eCollection 2021.
• Zaidat OO, Bozorgchami H, Ribo M, Saver JL, Mattle HP, Chapot R, Narata AP, Francois O, Jadhav AP, Grossberg JA, Riedel CH, Tomasello A, Clark WM, Nordmeyer H, Lin E, Nogueira RG, Yoo AJ, Jovin TG, Siddiqui AH, Bernard T, Claffey M, Andersson T. Primary Results of the Multicenter ARISE II Study (Analysis of Revascularization in Ischemic Stroke With EmboTrap). Stroke. 2018 May;49(5):1107-1115. doi: 10.1161/STROKEAHA.117.020125. Epub 2018 Apr 11.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 20, 2016): 228
• Original Enrollment: Not Provided
• Actual Study Completion Date: September 2017
• Actual Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. The patient or the patient's legally authorized representative has signed and dated an Informed Consent Form.
2. Aged between 18 years and 85 years (inclusive).
3. A new focal disabling neurologic deficit consistent with acute cerebral ischemia.
4. NIHSS score ≥8 and ≤25.
5. Pre-ictal mRS score of 0 or 1.
6. The interventionalist estimates that at least one deployment of the EmboTrap device can be completed within 8 hours from the onset of symptoms.
7. Patients for whom IV-tPA is indicated and who are available for treatment, are treated with IV-tPA.
8. IV-tPA, if used, was initiated within 3 hrs of stroke onset (onset time is defined as the last time when the patient was witnessed to be at baseline), with investigator verification that the subject has received/is receiving the correct IV t-PA dose for the estimated weight.
9. Angiographic confirmation of an occlusion of an ICA (including T or L occlusions), M1 or M2 MCA, VA, or BA with mTICI flow of 0 - 1.

10. For strokes in the anterior circulation the following imaging criteria should also be met:

    1. MRI criterion: volume of diffusion restriction visually assessed ≤50 mL. OR
    2. CT criterion: ASPECTS 6 to 10 on baseline CT or CTA-source images, or, volume of significantly lowered CBV ≤50 mL.
11. The patient is indicated for neurothrombectomy treatment by the interventionalist and it is confirmed by diagnostic angiography that the device will be able to reach the target lesion proximally.

Exclusion Criteria:

1. Life expectancy likely less than 6 months.
2. Females who are pregnant or breastfeeding.
3. History of severe allergy to contrast medium.
4. Known nickel allergy at time of treatment.
5. Known current use of cocaine at time of treatment.
6. Patient has suffered a stroke in the past 3 months.
7. The patient presents with an NIHSS score <8 or >25 or is physician assessed as being in a clinically relevant uninterrupted coma.
8. Subject participating in another study involving an investigational device or drug.
9. Use of warfarin anticoagulation or any Novel Anticoagulant with International Normalized Ratio (INR) >3.0.
10. Platelet count <50,000/μL.
11. Glucose <50 mg/dL.
12. Any known hemorrhagic or coagulation deficiency.
13. Unstable renal failure with serum creatinine >3.0 or Glomerular Filtration Rate (GFR) <30.
14. Patients who have received a direct thrombin inhibitor within the last 48 hours; must have a partial thromboplastin time (PTT) less than 1.5 times the normal to be eligible.
15. All patients with severe hypertension on presentation (SBP> 220mmHg and/or DBP>120mmHg). All patients, in whom intravenous therapy with blood pressure medications is indicated, with hypertension that remains severe and sustained despite intravenous therapy (SBP >185mmHg and/or DBP>110mmHg). .
16. Known cerebral vasculitis.
17. Rapidly improving neurological status.
18. Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.
19. Ongoing seizure due to stroke.
20. Evidence of active systemic infection.
21. Known cancer with metastases.
22. Computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of recent/ fresh hemorrhage on presentation.
23. Baseline computed tomography (CT) or MRI showing mass effect or intracranial tumor (except small meningioma).
24. Suspicion of aortic dissection, presumed septic embolus, or suspicion of bacterial endocarditis.
25. Stenosis, or any occlusion, in a proximal vessel that requires treatment or prevents access to the site of occlusion.
26. Evidence of dissection in the extra or intracranial cerebral arteries.
27. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Germany, Ireland, United States

Administrative Information

• NCT Number: NCT02488915
• Other Study ID Numbers: CIP002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Neuravi Inc.
• Original Responsible Party: [Redacted]
• Current Study Sponsor: Neuravi Inc.
• Original Study Sponsor: [Redacted]
• Collaborators: Not Provided

Investigators

• Principal Investigator: Prof. Sam Zaidat, M.D.; St. Vincent Mercy Mercy Hospital, Toledo,Ohio, USA
• Principal Investigator: Prof. Tommy Andersson, M.D.; Karolinska Institutet
• Study Director: Prof. Jeffery Saver, M.D.; UCLA, CA, USA.
• Study Director: Prof. Heinrich Mattle, M.D.; University of Berne, Berne, Switzerland.

• PRS Account: Neuravi Inc.
• Verification Date: June 2018