DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With Endovascular Clot Retrieval
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Other: Direct endovascular clot retrieval Endovascular clot retrieval (ECR) within 4.5 hours stroke |
Other: Direct endovascular clot retrieval
Direct endovascular clot retrieval within 4.5 hours of stroke onset
|
Other: 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 |
Other: Bridging thrombolysis followed by ECR
Bridging thrombolysis followed by ECR within 4.5 hours of stroke onset
|
Outcome Measures
Primary Outcome Measures
- Modified Rankin Scale (mRS)- ordinal analysis [3 months]
Modified Rankin Scale (mRS) 0-2 or no change from baseline
Secondary Outcome Measures
- modified Rankin Scale (mRS)- ordinal analysis [3 months]
mRS 0-1 or no change from baseline
- Death [3 months]
Death due to any cause
- Angiographic reperfusion [Baseline]
Proportion of patients with good angiographic reperfusion (mTICI 2b-3)
- Symptomatic intracranial haemorrhage (sICH) [24 hours]
Proportion of patients with sICH
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
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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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Liverpool Hospital | Liverpool | New South Wales | Australia | 2170 |
2 | John Hunter Hospital | New Lambton | New South Wales | Australia | 2305 |
3 | Royal North Shore Hospital | St Leonards | New South Wales | Australia | 2605 |
4 | Royal Brisbane & Women's Hospital | Brisbane | Queensland | Australia | |
5 | Gold Coast University Hospital | Gold Coast | Queensland | Australia | 4215 |
6 | Princess Alexandra Hospital | Woolloongabba | Queensland | Australia | 4102 |
7 | Royal Adelaide Hospital | Adelaide | South Australia | Australia | 5000 |
8 | Monash Medical Centre | Clayton | Victoria | Australia | 3168 |
9 | Mobile Stroke Unit | Melbourne | Victoria | Australia | 3050 |
10 | Royal Melbourne Hospital | Melbourne | Victoria | Australia | |
11 | Fiona Stanley Hospital | Murdoch | Western Australia | Australia | 6150 |
12 | Sir Charles Gairdner Hospital | Nedlands | Western Australia | Australia | 6009 |
13 | Shantou Central Hospital | Shantou | Guangdong | China | |
14 | Cangzhou Central Hospital | Cangzhou | Hebei | China | |
15 | Wuhan Central Hospital | Wuhan | Hubei | China | |
16 | The 4th Affiliated Hospital of CMU | Shenyang | Liaoning | China | |
17 | Linyi People's Hospital | Linyi | Shandong | China | |
18 | Shanxi People's Hospital | Shanxi | Taiyuan | China | |
19 | Beijing Fengtai Youanmen Hospital | Beijing | China | ||
20 | Beijing Tiantin Hospital | Beijing | China | ||
21 | Yunfu People's Hospital | Guangdong | China | ||
22 | Shiyan Taihe Hospital | Hubei | China | ||
23 | Ningxiang People's Hospital | Hunan | China | ||
24 | China-Japan Union Hospital of Jilin University | Jilin | China | ||
25 | Maoming People's Hospital | Maoming | China | ||
26 | Binzhou People's Hospital | Shandong | China | ||
27 | Shunde Hospital of Southern Medical University | Shunde | China | ||
28 | Jingjiang People's Hospital | Taizhou | China | ||
29 | Tianjin TEDA Hospital | Tianjin | China | ||
30 | Singapore General Hospital | Singapore | Singapore | 169608 | |
31 | Bach Mai Hospital | Hanoi | Vietnam | ||
32 | Military Hospital 103 | Hanoi | Vietnam | ||
33 | 115 People's Hospital | Ho Chi Minh City | Vietnam |
Sponsors and Collaborators
- Neuroscience Trials Australia
- The Florey Institute of Neuroscience and Mental Health
Investigators
- Principal Investigator: Peter Mitchell, MD, Melbourne Health
- Principal Investigator: Bernard Yan, MD, Melbourne Health
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NTA1601