Randomization of Endovascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke Due to Large VEssel OcclusioN Trial
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Stroke
- Sponsor
- Hospital de Clinicas de Porto Alegre
- Enrollment
- 221
- Locations
- 15
- Primary Endpoint
- Distribution of the modified Rankin Scale scores (shift analysis)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
SHEILA CRISTINA OURIQUES MARTINS
MD, PHD, Stroke Neurologist
Hospital de Clinicas de Porto Alegre
Eligibility Criteria
Inclusion Criteria
- •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.
- •No significant pre-stroke functional disability (mRS ≤ 1)
- •Baseline NIHSS score obtained prior to randomization must be equal or higher than 8 points
- •Age ≥18 years
- •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.
- •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.
- •Informed consent obtained from patient or acceptable patient surrogate
Exclusion Criteria
- •Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR \> 3.0
- •Baseline platelet count \< 30.000/µL
- •Baseline blood glucose of \< 50mg/dL or \> 400mg/dl
- •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.
- •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).
- •Seizures at stroke onset which would preclude obtaining a baseline NIHSS
- •Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.
- •History of life threatening allergy (more than rash) to contrast medium
- •Subjects who has received IV t-PA treatment beyond 4,5 hours from the beginning of the symptoms
- •Woman of childbearing potential who is known to be pregnant or lactating or who has a positive pregnancy test on admission.
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Mortality(90 days)
- Functional independence (modified Rankin Score ≤ 2)(90 days)
- Infarct Burden at 24 hours(24 hours)
- Dramatic early favorable response(24 hours)
- Cost effectiveness(Life-time horizon perspective)
- Quality of life analysis(3 months, 6 months, 1 year)
- Vessel recanalization at 24 hours(24 hours)
- Successful recanalization at the end of procedure(immediatelly after procedure (only thrombectomy arm))
- Symptomatic Intracranial hemorrhage(24 hours)
- Procedure related complications(During the procedure)