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

Neuroscience Trials Australia

Status and phase: Completed; Phase 3

Conditions: Ischemic Stroke

Treatments: Other: Bridging thrombolysis followed by ECR; Other: Direct endovascular clot retrieval

Study type: Interventional

Funder types: Other

Identifiers

NCT03494920

NTA1601

Details and patient eligibility

About

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.

Full 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.

Enrollment: 295 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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295 participants in 2 patient groups

Direct endovascular clot retrieval

Other group

Description:

Endovascular clot retrieval (ECR) within 4.5 hours stroke

Treatment:

Other: Direct endovascular clot retrieval

Bridging thrombolysis followed by ECR

Other group

Description:

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

Treatment:

Other: Bridging thrombolysis followed by ECR