Randomization of Endovascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke Due to Large VEssel OcclusioN Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 221
- 试验地点
- 16
- 主要终点
- Distribution of the modified Rankin Scale scores (shift analysis)
研究概览
简要总结
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%.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •Subject participating in a study involving an investigational drug or device that would impact this study.
- •Cerebral vasculitis
- •Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤
- •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.)
- •Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas).
- •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.
- •Collaterals with malignant profile on CTA (without colateral circulation on CTA)
- •CT or MR evidence of hemorrhage (the presence of GRE microbleeds is allowed).
- •Significant mass effect with midline shift.
- •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
- •Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)
- •Evidence of intracranial tumor (except small meningioma).
结局指标
主要结局
Distribution of the modified Rankin Scale scores (shift analysis)
时间窗: 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
次要结局
- 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)
研究者
SHEILA CRISTINA OURIQUES MARTINS
MD, PHD, Stroke Neurologist
Hospital de Clinicas de Porto Alegre