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EndoVascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke (RESILIENT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02216643
Recruitment Status : Completed
First Posted : August 15, 2014
Last Update Posted : February 19, 2020
Sponsor:
Collaborators:
Ministry of Health, Brazil
Medtronic
Penumbra Inc.
iSchemaView, Inc
Brainomix Limited
Information provided by (Responsible Party):
SHEILA CRISTINA OURIQUES MARTINS, Hospital de Clinicas de Porto Alegre

Tracking Information
First Submitted Date  ICMJE August 13, 2014
First Posted Date  ICMJE August 15, 2014
Last Update Posted Date February 19, 2020
Actual Study Start Date  ICMJE February 8, 2017
Actual Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2014)
Distribution of the modified Rankin Scale scores (shift analysis) [ Time Frame: 90 days ]
Distribution of the modified Rankin Scale scores at 90 days (shift analysis) as evaluated by two separate assessors who are blinded to treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2020)
  • Functional independence (modified Rankin Score ≤ 2) [ Time Frame: 90 days ]
    Functional independence measured by modified Rankin Score ≤ 2 in 90 days in both groups
  • Infarct Burden at 24 hours [ Time Frame: 24 hours ]
    ASPECTS change from baseline to 24 hours on CT or MRI
  • Dramatic early favorable response [ Time Frame: 24 hours ]
    defined as an NIHSS score 0-2 or a NIHSS score decrease of ≥8 from baseline at 24 hours
  • Cost effectiveness [ Time Frame: Life-time horizon perspective ]
    Cost effectiveness analysis of interventional therapy vs medical therapy alone
  • Quality of life analysis [ Time Frame: 3 months, 6 months, 1 year ]
    Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year, between interventional therapy vs medical therapy alone
  • Vessel recanalization at 24 hours [ Time Frame: 24 hours ]
    Vessel recanalization evaluated by CT angiography (CTA) or MR angiography (MRA) at 24 hours in both treatment groups
  • Successful recanalization at the end of procedure [ Time Frame: immediatelly after procedure (only thrombectomy arm) ]
    defined as a grade of 2b or 3 (indicating reperfusion of >50% of the affected territory) on the modified Thrombolysis in Cerebral Infarction (mTICI) scale
  • Mortality [ Time Frame: 90 days ]
    Mortality at 90 days
  • Symptomatic Intracranial hemorrhage [ Time Frame: 24 hours ]
    Clinically significant Intracranial hemorrhage (ICH) rates at 24 (-2/+12) hours. All intracerebral hemorrhages will be classified by a central core-lab using the ECASS criteria for CT evaluation. Symptomatic ICH will be defined as per the SITS-MOST definition: deterioration in NIHSS score of ≥4 points within 24 hours from treatment and evidence of intraparenchymal hemorrhage type 2 in the 22 to 36 hours follow-up imaging scans. The incidence of any asymptomatic hemorrhage measured at 24 (-2/+12) hours will also be compared
  • Procedure related complications [ Time Frame: During the procedure ]
    Complications occurring during the procedure will be evaluated: distal embolization in a new territory, arterial dissection, arterial perfuration, groin hematoma
Original Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2014)
  • Functional independence (modified Rankin Score ≤ 2) [ Time Frame: 90 days ]
    Functional independence measured by modified Rankin Score ≤ 2 in 90 days in both groups
  • Vessel recanalization [ Time Frame: 24 hours ]
    Vessel recanalization evaluated by Computed Tomography angiography or Magnetic Resonance Angiography at 24 hours in both treatment groups
  • Quality of life [ Time Frame: 3 months, 6 months, 1 year ]
    Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year, between interventional therapy vs medical therapy alone
  • Cost effectiveness [ Time Frame: 90 days ]
    Cost effectiveness analysis of interventional therapy vs medical therapy alone
  • Mortality [ Time Frame: 90 days ]
    Mortality at 90 days
  • Symptomatic Intracranial hemorrhage [ Time Frame: 24 hours ]
    Clinically significant Intracranial hemorrhage (ICH) rates at 24 (-2/+12) hours. All intracerebral hemorrhages will be classified by a central core-lab using the ECASS criteria. Symptomatic ICH will be defined as per the SITS-MOST definition: deterioration in NIHSS score of ≥4 points within 24 hours from treatment and evidence of intraparenchymal hemorrhage type 2 in the 22 to 36 hours follow-up imaging scans. The incidence of any asymptomatic hemorrhage measured at 24 (-2/+12) hours will also be compared
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE EndoVascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke
Official Title  ICMJE Randomization of Endovascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke Due to Large VEssel OcclusioN Trial
Brief Summary Prospective, multi-center, randomized, controlled, open, blinded-endpoint trial with a sequential design. The randomization employs a 1:1 ratio of mechanical thrombectomy with stentriever and/or Thromboaspiration versus medical management alone. Randomization will be done under a minimization process using age, baseline NIHSS, use of IV tpa, vessel occlusion site and hospital. To evaluate the hypothesis that mechanical thrombectomy is superior to medical management alone in achieving more favorable outcomes in the distribution of the modified Rankin Scale scores at 90 days in subjects presenting with acute large vessel ischemic stroke <8 hours from symptom onset. Subjects are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization. Sample size is projected to be 690 patients for a difference in treatment effect of 10%.
Detailed Description

Patients with acute ischemic stroke related to anterior circulation large vessel occlusion will be randomized up to 8 hours from symptoms onset in both arms (mechanical thrombectomy versus medical management alone). Subjects are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization. They will be admitted at acute stroke units in Brazil (or ICU if needed) and treated following international guidelines. Concomitant medications and non-pharmacological therapies will be recorded. A maximum of six attempts to retrieve the thrombus in a single vessel can be made. No additional treatment will be allowed either with Intrarterial tPA, mechanical devices or angioplasty/stenting.

The primary endpoint will be distribution of the modified Rankin Scale scores at 90 days (shift analysis) as evaluated by two separate assessors who are blinded to treatment

Interim Analysis The sample size for this Phase III Trial is projected to be 690 subjects. For interim analyses, the method of Lan and DeMets will be used to allocate alpha via the power family method with φ (phi) equal to 1 for the assessment of efficacy and futility, respectively after the first 174, 346 and 518 patients enrolled have completed the 90-day follow-up. The interval may be more frequent if requested by the Data and Safety Monitoring Board (DSMB). At interim analysis, in case the stopping boundaries are crossed the DSMB may recommend stopping the study either for better efficacy of the tested treatment either for futility. Other factors, such as safety, will be taken into consideration by the DSMB in the decision to stop the study. When considering stopping the trial for safety reasons, the DSMB will be instructed to consider both mortality (mRS=6) and severe dependency (mRS=5) at 3 months as one single outcome.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Stroke
  • Ischemic Stroke
Intervention  ICMJE
  • Procedure: Thrombectomy
    Patients with acute ischemic stroke with anterior circulation large vessel occlusion will be randomized to receive mechanical thrombectomy with stent-retriever Solitaire FR® and/or thromboaspiration with Penumbra System® versus medical management alone versus medical management alone. A maximum of six attempts to retrieve the thrombus in a single vessel can be made . No additional treatment will be allowed either with IA tPA, other mechanical devices or angioplasty/stenting.
    Other Names:
    • Endovascular treatment
    • Intrarterial treatment
    • Endovascular revascularization
  • Device: Stentriever Solitaire FR® or Penumbra System®
    Patients with acute ischemic stroke with anterior circulation large vessel occlusion will be randomized to receive mechanical thrombectomy with stent-retriever and/or thromboaspiration versus medical management alone versus medical management alone. A maximum of six attempts to retrieve the thrombus in a single vessel can be made . No additional treatment will be allowed either with IA tPA, other mechanical devices or angioplasty/stenting.
Study Arms  ICMJE
  • Experimental: thrombectomy
    mechanical thrombectomy with stentriever Solitaire FR® and/or thromboaspiration with Penumbra System® in patients with large vessel occlusion in cerebral anterior circulation vessels
    Interventions:
    • Procedure: Thrombectomy
    • Device: Stentriever Solitaire FR® or Penumbra System®
  • No Intervention: best medical treatment
    best medical treatment in patients with acute ischemic stroke with anterior circulation large vessel occlusion
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 6, 2020)
221
Original Estimated Enrollment  ICMJE
 (submitted: August 13, 2014)
690
Actual Study Completion Date  ICMJE June 30, 2019
Actual Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Acute ischemic stroke where patient is ineligible for IV thrombolytic treatment or the treatment is contraindicated (e.g., subject presents beyond recommended time from symptom onset), or where patient has received IV thrombolytic therapy without clinical improvement.
  2. No significant pre-stroke functional disability (mRS ≤ 1)
  3. Baseline NIHSS score obtained prior to randomization must be equal or higher than 8 points
  4. Age ≥18 years
  5. Occlusion (TICI 0-1) of the intracranial ICA (distal ICA or T occlusions) and/or MCA-M1 segment suitable for endovascular treatment, as evidenced by CTA, MRA or angiogram, with or without concomitant cervical carotid occlusion or stenosis.
  6. Patient treatable within eight hours of symptom onset. Symptoms onset is defined as point in time the patient was last seen well (at baseline). Treatment start is defined as groin puncture.
  7. Informed consent obtained from patient or acceptable patient surrogate

Exclusion Criteria:

  1. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 3.0
  2. Baseline platelet count < 30.000/µL
  3. Baseline blood glucose of < 50mg/dL or > 400mg/dl
  4. Severe, sustained hypertension (SBP > 185 mm Hg or DBP > 110 mm Hg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using AHA guidelines recommended medication (including iv antihypertensive drips), the patient can be enrolled.
  5. Patients in coma (NIHSS item of consciousness >1) (Intubated patients for transfer could be randomized only in case an NIHSS is obtained by a neurologist prior transportation).
  6. Seizures at stroke onset which would preclude obtaining a baseline NIHSS
  7. Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.
  8. History of life threatening allergy (more than rash) to contrast medium
  9. Subjects who has received IV t-PA treatment beyond 4,5 hours from the beginning of the symptoms
  10. Woman of childbearing potential who is known to be pregnant or lactating or who has a positive pregnancy test on admission.
  11. Subject participating in a study involving an investigational drug or device that would impact this study.
  12. Cerebral vasculitis
  13. Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤1. This excludes patients who are severely demented, require constant assistance in a nursing home type setting or who live at home but are not fully independent in activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.)
  14. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas).
  15. Hypodensity on CT or restricted diffusion amounting to an ASPECTS score of <6 on NCCT, or <5 on DWI MRI. The use of CTP or MRI perfusion is optional.
  16. Collaterals with malignant profile on CTA (without colateral circulation on CTA)
  17. CT or MR evidence of hemorrhage (the presence of GRE microbleeds is allowed).
  18. Significant mass effect with midline shift.
  19. Evidence of ipsilateral carotid occlusion, high grade stenosis or arterial dissection in the extracranial or petrous segment of the internal carotid artery that cannot be treated or will prevent access to the intracranial clot or excessive tortuosity of cervical vessels precluding device delivery/deployment
  20. Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)
  21. Evidence of intracranial tumor (except small meningioma).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02216643
Other Study ID Numbers  ICMJE 22042613.6.1001.5327
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party SHEILA CRISTINA OURIQUES MARTINS, Hospital de Clinicas de Porto Alegre
Study Sponsor  ICMJE Hospital de Clinicas de Porto Alegre
Collaborators  ICMJE
  • Ministry of Health, Brazil
  • Medtronic
  • Penumbra Inc.
  • iSchemaView, Inc
  • Brainomix Limited
Investigators  ICMJE
Principal Investigator: Raul Nogueira, MD Emory University
Principal Investigator: Sheila CO Martins, MD Hospital de Clínicas de Porto Alegre
PRS Account Hospital de Clinicas de Porto Alegre
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP