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

Not yet recruiting

Phase 3 Results N/A

Trial Description

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.

Conditions

Interventions

  • Thrombectomy Device
    Other Names: Mechanical thrombectomy
    Intervention Desc: Patients with acute ischemic stroke with anterior circulation large vessel occlusion will be randomized to receive mechanical thrombectomy with stent-retriever Solitaire 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.
    ARM 1: Kind: Experimental
    Label: thrombectomy
    Description: mechanical thrombectomy with the Solitaire FR device in patients with large vessel occlusion in cerebral anterior circulation vessels
    ARM 2: Kind: Experimental
    Label: thrombectomy (Solitaire and/or Penumbra)
    Description: mechanical thrombectomy with stentriever Solitaire and/or thromboaspiration with Penumbra System in patients with large vessel occlusion in cerebral anterior circulation vessels
  • Stentriever Solitaire FR® Device
    Intervention Desc: Patients with acute ischemic stroke with anterior circulation large vessel occlusion will be randomized to receive mechanical thrombectomy with the approved stentriever stentriever Solitaire FR® versus medical management alone. A maximum of six attempts to retrieve the thrombus in a single vessel can be made with any Solitaire FR device. No additional treatment will be allowed either with IA tPA, mechanical devices or angioplasty/stenting.
    ARM 1: Kind: Experimental
    Label: thrombectomy
    Description: mechanical thrombectomy with the Solitaire FR device in patients with large vessel occlusion in cerebral anterior circulation vessels
  • Stentriever Solitaire or Penumbra System Device
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: thrombectomy (Solitaire and/or Penumbra)
    Description: mechanical thrombectomy with stentriever Solitaire and/or thromboaspiration with Penumbra System in patients with large vessel occlusion in cerebral anterior circulation vessels

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Distribution of the modified Rankin Scale scores (shift analysis) 90 days No
Secondary Functional independence (modified Rankin Score ≤ 2) 90 days No
Secondary Vessel recanalization 24 hours No
Secondary Quality of life 3 months, 6 months, 1 year No
Secondary Cost effectiveness 90 days No
Secondary Mortality 90 days Yes
Secondary Symptomatic Intracranial hemorrhage 24 hours Yes

Sponsors