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

Conditions

Ischemic Stroke

Keywords

Stroke, Ischemia, Cerebral Infarction, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases, Pathologic Processes, Brain Infarction, Brain Ischemia, Tissue Plasminogen Activator, Plasminogen, Fibrinolytic Agents, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action

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.

Mitchell PJ, Yan B, Churilov L, Dowling RJ, Bush SJ, Bivard A, Huo XC, Wang G, Zhang SY, Ton MD, Cordato DJ, Kleinig TJ, Ma H, Chandra RV, Brown H, Campbell BCV, Cheung AK, Steinfort B, Scroop R, Redmond K, Miteff F, Liu Y, Duc DP, Rice H, Parsons MW, Wu TY, Nguyen HT, Donnan GA, Miao ZR, Davis SM, DIRECT-SAFE Investigators.

2022-07-01160 citations

10.1016/s0140-6736(22)00564-5

DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval versus Standard Bridging Therapy

Peter Mitchell, Bernard Yan, Leonid Churilov, Richard Dowling, Steven Bush et al. (11 authors)

Journal of Stroke2022-01-3137 citations

10.5853/jos.2021.03475

Direct thrombectomy versus bridging thrombolysis with mechanical thrombectomy in middle cerebral artery stroke: a real-world analysis through National Inpatient Sample data

Sandeep Kandregula, Amey Savardekar, Pankaj Sharma, Jerry McLarty, Jennifer Kosty et al. (8 authors)

Neurosurgical FOCUS2021-07-0122 citations

10.3171/2021.4.focus21132

MR CLEAN-NO IV: intravenous treatment followed by endovascular treatment versus direct endovascular treatment for acute ischemic stroke caused by a proximal intracranial occlusion-study protocol for a randomized clinical trial.

Treurniet KM, LeCouffe NE, Kappelhof M, Emmer BJ, van Es ACGM, Boiten J, Lycklama GJ, Keizer K, Yo LSF, Lingsma HF, van Zwam WH, de Ridder I, van Oostenbrugge RJ, van der Lugt A, Dippel DWJ, Coutinho JM, Roos YBWEM, Majoie CBLM, MR CLEAN-NO IV Investigators.

2021-02-1545 citations

10.1186/s13063-021-05063-5

Interventions

OTHERDirect endovascular clot retrieval

Direct endovascular clot retrieval within 4.5 hours of stroke onset

OTHERBridging thrombolysis followed by ECR

Bridging thrombolysis followed by ECR within 4.5 hours of stroke onset

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Masking description

Blinded core laboratory adjudications of the primary outcome. NIHSS and mRS (secondary outcomes) performed by blinded assessor.

Intervention model description

Patients will be randomised to either direct endovascular clot retrieval or to bridging intravenous thrombolysis with endovascular clot retrieval.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Modified Rankin Scale (mRS)- ordinal analysis	3 months	Modified Rankin Scale (mRS) 0-2 or no change from baseline

Secondary

Measure	Time frame	Description
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

Countries

Australia, China, Singapore, Vietnam

Outcome results

None listed