DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With Endovascular Clot Retrieval

Phase 3

Completed

• Conditions: Ischemic Stroke

• 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.

Study Timeline

• Study First Submitted: 2018-04-04
• Study First Submitted QC: 2018-04-04
• Study First Posted: 2018-04-11
• Study Start: 2018-04-27
• Status Verified: 2021-07
• Primary Completion: 2021-09-08
• Study Completion: 2021-09-08
• Last Update Submitted: 2022-06-14
• Last Update Posted: 2022-06-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 295

Inclusion Criteria

1. Patients presenting with acute ischemic stroke eligible using standard criteria to receive IV thrombolysis within 4.5 hours of stroke onset
2. Patient's age is ≥18 years
3. Intra-arterial clot retrieval treatment can commence (groin puncture) within 6 hours of stroke onset.
4. Arterial occlusion on CTA or MRA of the ICA, M1, M2 or basilar artery

Exclusion Criteria

1. Intracranial hemorrhage (ICH) identified by CT or MRI
2. Rapidly improving symptoms at the discretion of the investigator
3. Pre-stroke mRS score of ≥ 4 (indicating previous disability)
4. Hypodensity in >1/3 MCA territory on non-contrast CT
5. Contra indication to imaging with contrast agents
6. Any terminal illness such that patient would not be expected to survive more than 1 year
7. 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.
8. Pregnant women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

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)

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

John Hunter Hospital; 🇦🇺 New Lambton, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 St Leonards, New South Wales, Australia

Royal Brisbane & Women's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Gold Coast University Hospital; 🇦🇺 Gold Coast, Queensland, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Monash Medical Centre; 🇦🇺 Clayton, Victoria, Australia

Mobile Stroke Unit; 🇦🇺 Melbourne, Victoria, Australia

Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia

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