DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With Endovascular Clot Retrieval
- Conditions
- Ischemic Stroke
- Interventions
- Other: Direct endovascular clot retrievalOther: Bridging thrombolysis followed by ECR
- Registration Number
- NCT03494920
- Lead Sponsor
- Neuroscience Trials Australia
- Brief Summary
The study will be a multicentre, prospective, randomized, open label, blinded endpoint (PROBE) phase 3 trial (2 arm with 1:1 randomization) in ischemic stroke patients within 4.5 hours of stroke onset. Randomised patients will be stratified for site of baseline arterial occlusion into one of three groups: 1. internal carotid artery (ICA) 2. middle cerebral artery (MCA) 3. basilar artery (BA). Patients will be randomised to either bridging intravenous thrombolysis with endovascular clot retrieval (ECR), or direct endovascular clot retrieval.
- Detailed Description
The DIRECT-SAFE trial will include patients with acute ischemic stroke, who are ≥18 years of age and are eligible for standard intravenous tPA therapy within 4.5 hours of stroke onset. Patients will be assessed for large vessel occlusion to determine their eligibility for randomization into the trial. Eligible vessel occlusions include the internal carotid artery, basilar artery or middle cerebral artery (M1 or M2). Patients will be consented after large vessel occlusion is confirmed based on standard care multimodal imaging.
Patients will be recruited in Australia, New Zealand, China, Taiwan, Vietnam, Singapore and Europe. Randomisation either direct to ECR or standard thrombolytic therapy and ECR shall be in a 1:1 ratio.
All patients will have a multimodal MR (or CT/CTP at investigator's discretion if MRI not possible) at 18 to 30 hours post treatment to assess reperfusion, recanalization, ischemic core growth and hemorrhagic transformation. Final follow up will occur at Day 90.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 295
- Patients presenting with acute ischemic stroke eligible using standard criteria to receive IV thrombolysis within 4.5 hours of stroke onset
- Patient's age is ≥18 years
- Intra-arterial clot retrieval treatment can commence (groin puncture) within 6 hours of stroke onset.
- Arterial occlusion on CTA or MRA of the ICA, M1, M2 or basilar artery
- Intracranial hemorrhage (ICH) identified by CT or MRI
- Rapidly improving symptoms at the discretion of the investigator
- Pre-stroke mRS score of ≥ 4 (indicating previous disability)
- Hypodensity in >1/3 MCA territory on non-contrast CT
- Contra indication to imaging with contrast agents
- Any terminal illness such that patient would not be expected to survive more than 1 year
- 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.
- Pregnant women
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Direct endovascular clot retrieval Direct endovascular clot retrieval Endovascular clot retrieval (ECR) within 4.5 hours stroke Bridging thrombolysis followed by ECR Bridging thrombolysis followed by ECR Intravenous tPA (at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour) followed by ECR
- Primary Outcome Measures
Name Time Method Modified Rankin Scale (mRS)- ordinal analysis 3 months Modified Rankin Scale (mRS) 0-2 or no change from baseline
- Secondary Outcome Measures
Name Time Method Angiographic reperfusion Baseline Proportion of patients with good angiographic reperfusion (mTICI 2b-3)
modified Rankin Scale (mRS)- ordinal analysis 3 months mRS 0-1 or no change from baseline
Death 3 months Death due to any cause
Symptomatic intracranial haemorrhage (sICH) 24 hours Proportion of patients with sICH
Trial Locations
- Locations (33)
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Shanxi People's Hospital
🇨🇳Shanxi, Taiyuan, China
China-Japan Union Hospital of Jilin University
🇨🇳Jilin, China
Wuhan Central Hospital
🇨🇳Wuhan, Hubei, China
John Hunter Hospital
🇦🇺New Lambton, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Shiyan Taihe Hospital
🇨🇳Hubei, China
Beijing Fengtai Youanmen Hospital
🇨🇳Beijing, China
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Maoming People's Hospital
🇨🇳Maoming, China
Binzhou People's Hospital
🇨🇳Shandong, China
Shunde Hospital of Southern Medical University
🇨🇳Shunde, China
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Mobile Stroke Unit
🇦🇺Melbourne, Victoria, Australia
Shantou Central Hospital
🇨🇳Shantou, Guangdong, China
Cangzhou Central Hospital
🇨🇳Cangzhou, Hebei, China
The 4th Affiliated Hospital of CMU
🇨🇳Shenyang, Liaoning, China
Ningxiang People's Hospital
🇨🇳Hunan, China
Tianjin TEDA Hospital
🇨🇳Tianjin, China
Jingjiang People's Hospital
🇨🇳Taizhou, China
Gold Coast University Hospital
🇦🇺Gold Coast, Queensland, Australia
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Linyi People's Hospital
🇨🇳Linyi, Shandong, China
Yunfu People's Hospital
🇨🇳Guangdong, China
Beijing Tiantin Hospital
🇨🇳Beijing, China
Military Hospital 103
🇻🇳Hanoi, Vietnam
Singapore General Hospital
🇸🇬Singapore, Singapore
Bach Mai Hospital
🇻🇳Hanoi, Vietnam
115 People's Hospital
🇻🇳Ho Chi Minh City, Vietnam
Royal Brisbane & Women's Hospital
🇦🇺Brisbane, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia