Randomised Trial of Biosimilar TNK Versus TPA during Endovascular Therapy For Acute Ischemic Stroke Due To Large Vessel Occlusions: RE-OPEN.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 372
- 试验地点
- 17
- 主要终点
- 1) Proportion of patients who will be independent at 3 months ( using modified Rankin score; mRS less than or equal to 2 taken as a good outcome)
研究概览
简要总结
Acute ischemic stroke (AIS) due to large vessel occlusions (LVO) is a serious and potentially disabling situation. Although there have been issue with terminology, blockages of the intracranial internal carotid artery (ICA), proximal posterior, middle, and anterior cerebral arteries (PCA, MCA, and ACA, respectively), intracranial vertebral artery (VA), and/or basilar artery (BA) are commonly referred to as large vessel occlusions (LVOs). Accounting for up to 46% of acute ischemic strokes (AISs), LVOs possess outsized clinical importance as they more than doubled the risk of death or dependence as compared to non-LVO AISs in the pre-endovascular era. Rapid and timely treatment with intravenous (IV) thrombolysis and endovascular treatment (EVT) leading to vessel recanalization improves patient outcomes significantly and bridging therapy is the current standard of care in comprehensive stroke centres across the world and in India. However, an incompletely answered question is whether one thrombolytic agent is better over another during the bridging therapy. There has been a debate if Tenecteplase (TNK) is superior to rTPA (recombinant tissue plasminogen activator, Alteplase) as a thrombolytic agent. The current study aims to understand if one agent is superior to the other during bridging therapy in the treatment of AIS due to LVO’s. Eligible patients with AIS and LVO, presenting within 4.5 hours, will be randomised to either receive rTPA or TNK in standard doses before undergoing endovascular thrombectomy. Primary outcomes include Proportion of patients who will be independent at 3 months ( using modified Rankin score; mRS less than or equal to 2 taken as a good outcome) and proportion of patients who achieve recanalization TICI grade 2b or 3 at first angiography run and end of the EVT procedure. Secondary outcomes include proportion of patients with early Neurological improvement (ENI) defined as improvement of NIHSS by 4 points at 24 hours, rate of symptomatic ICH as defined using SITS MOST criteria, rate of any ICH, rate of any systemic major or minor bleeding using GUSTO classification, and duration of hospital stay.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Age 18 years and above.
- •Patients with Acute ischemic stroke 3) Within 4.5 hours of onset 4) NIHSS greater than or equal to 5 5) Presence of a proximal large vessel occlusion.
- •( M1 MCA, proximal M2 MCA, distal ICA, Basilar artery) on CTA/MRA.
- •Eligible for thrombolysis as per current inclusion and exclusion criteria.
- •Eligible for endovascular treatment as per the current protocol.
- •8 ) Agree for endovascular therapy as a part of standard treatment for LVO.
- •9 ) ASPECTS score (Alberta Stroke Program Early CT score) greater than or equal to 6 10) Informed and signed consent.
排除标准
- •1.Patients with intracerebral hemorrhage.
- •2.Hypodensity in greater than one third of MCA territory 3.Recent ischemic stroke within three months 4.ASPECTS less than
- •5.Recent past history or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm.
- •6.Current use of oral anticoagulation with Vitamin K antagonist with INR greater than or equal to 1.7 as per current guidelines.
- •7.Non-Availability of INR if patient is on Vitamin K antagonist.
- •8.Current use of novel oral anticoagulants (NOAC’s).
- •9.Active use of heparin in therapeutic doses.
- •10.Use of glycoprotein IIb-IIIa inhibitors within the past 72 hours.
- •11.Clinically significant hypoglycemia.
- •12.Persistently elevated blood pressure greater than 185 mmHg systolic or 110 mmHg diastolic (as per standard thrombolysis guidelines).
- •13.Hereditary or acquired hemorrhagic diathesis 14.Gastrointestinal or urinary bleeding within the preceding 21 days 15.Major surgery within the preceding 14 days which poses risk 16.Any recent cranial, spinal surgery within 3 months.
- •17.Baseline mRS greater than or equal to 2 18.Active Pregnancy 19.Contraindication to contrast agents 20.Intra-cardiac tumor.
- •Active Subacute bacterial endocarditis.
- •22.Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
结局指标
主要结局
1) Proportion of patients who will be independent at 3 months ( using modified Rankin score; mRS less than or equal to 2 taken as a good outcome)
时间窗: At the end of procedure | 3 months
2) Proportion of patients who achieve recanalization mTICI grade 2b or 3 at first angiography run.
时间窗: At the end of procedure | 3 months
次要结局
- 1. Proportion of patients who achieve mTICI grade 2b/3 (appendix 5) at the end of the EVT procedure.(2. Proportion of patients with early Neurological improvement (ENI) defined as improvement of NIHSS)