CompletedNCT03494920Updated Jun 16, 2022

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

A Phase 3 interventional study of Direct endovascular clot retrieval and Bridging thrombolysis followed by ECR in Ischemic Stroke, sponsored by Neuroscience Trials Australia. Completed at 33 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-06-16.

Sponsored by Neuroscience Trials Australia · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 295
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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.

Conditions studied

Ischemic Stroke

Browse trials for

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

In context

Ischemic Stroke

2,612 studies on the registry are indexed under Ischemic Stroke; 971 are open to participants now.

This study's enrollment of 295 is above the median of 120 across 1,776 interventional studies indexed under Ischemic Stroke.

Browse Ischemic Stroke studies →

Lead sponsor

Neuroscience Trials Australia is the lead sponsor of 12 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
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

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Single (Outcomes assessor)
Enrollment: 295 participants (actual)

Study arms

Other
Direct endovascular clot retrieval
Endovascular clot retrieval (ECR) within 4.5 hours stroke
Other: Direct endovascular clot retrieval
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

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

What researchers measure

Primary outcomes

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

Secondary outcomes

modified Rankin Scale (mRS)- ordinal analysis
mRS 0-1 or no change from baseline
Time frame: 3 months
Death
Death due to any cause
Time frame: 3 months
Angiographic reperfusion
Proportion of patients with good angiographic reperfusion (mTICI 2b-3)
Time frame: Baseline
Symptomatic intracranial haemorrhage (sICH)
Proportion of patients with sICH
Time frame: 24 hours

Study locations

33 sites

Liverpool Hospital
Liverpool, New South Wales 2170, Australia
John Hunter Hospital
New Lambton, New South Wales 2305, Australia
Royal North Shore Hospital
St Leonards, New South Wales 2605, Australia
Royal Brisbane & Women's Hospital
Brisbane, Queensland, Australia
Gold Coast University Hospital
Gold Coast, Queensland 4215, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland 4102, Australia
Royal Adelaide Hospital
Adelaide, South Australia 5000, Australia
Monash Medical Centre
Clayton, Victoria 3168, Australia
Mobile Stroke Unit
Melbourne, Victoria 3050, Australia
Royal Melbourne Hospital
Melbourne, Victoria, Australia
Fiona Stanley Hospital
Murdoch, Western Australia 6150, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia 6009, Australia
Shantou Central Hospital
Shantou, Guangdong, China
Cangzhou Central Hospital
Cangzhou, Hebei, China
Wuhan Central Hospital
Wuhan, Hubei, China
The 4th Affiliated Hospital of CMU
Shenyang, Liaoning, China
Linyi People's Hospital
Linyi, Shandong, China
Shanxi People's Hospital
Shanxi, Taiyuan, China
Beijing Fengtai Youanmen Hospital
Beijing, China
Beijing Tiantin Hospital
Beijing, China
Yunfu People's Hospital
Guangdong, China
Shiyan Taihe Hospital
Hubei, China
Ningxiang People's Hospital
Hunan, China
China-Japan Union Hospital of Jilin University
Jilin, China
Maoming People's Hospital
Maoming, China
Binzhou People's Hospital
Shandong, China
Shunde Hospital of Southern Medical University
Shunde, China
Jingjiang People's Hospital
Taizhou, China
Tianjin TEDA Hospital
Tianjin, China
Singapore General Hospital
Singapore, 169608, Singapore
Bach Mai Hospital
Hanoi, Vietnam
Military Hospital 103
Hanoi, Vietnam
115 People's Hospital
Ho Chi Minh City, Vietnam

References and documents

Publications

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. Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4.5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial. Lancet. 2022 Jul 9;400(10346):116-125. doi: 10.1016/S0140-6736(22)00564-5. PubMed 35810757 ↗
Mitchell PJ, Yan B, Churilov L, Dowling RJ, Bush S, Nguyen T, Campbell BCV, Donnan GA, Miao Z, Davis SM; DIRECT-SAFE Investigators. DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval versus Standard Bridging Therapy. J Stroke. 2022 Jan;24(1):57-64. doi: 10.5853/jos.2021.03475. Epub 2022 Jan 31. PubMed 35135060 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 16, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03494920
Lead sponsor: Neuroscience Trials Australia
Collaborators: The Florey Institute of Neuroscience and Mental Health
Responsible party: Sponsor
First posted: Apr 11, 2018
Start date: Apr 27, 2018
Primary completion: Sep 8, 2021
Completion: Sep 8, 2021
Last update: Jun 16, 2022

Study contacts

Peter Mitchell, MD

principal investigator · Melbourne Health

Bernard Yan, MD

principal investigator · Melbourne Health

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Ischemic Stroke →

Other studies from this sponsor

Neuroscience Trials Australia

Start the discussion