Ischemic StrokePhase 3NCT03494920
DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With Endovascular Clot Retrieval
A Phase 3 study testing Direct endovascular clot retrieval and Bridging thrombolysis followed by ECR in people with Ischemic Stroke, run by Neuroscience Trials Australia at 33 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- Direct endovascular clot retrieval and Bridging thrombolysis followed by ECR
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 295 participants
- Where
- 33 sitesin 4 countries
- Study dates
- 27 Apr 2018to 8 Sep 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
33 sites in 4 countries.
33 sites in 4 countries
China17 sites
Beijing Fengtai Youanmen Hospital
Beijing
Beijing Tiantin Hospital
Beijing
Cangzhou Central Hospital
Cangzhou, Hebei
Yunfu People's Hospital
Guangdong
Shiyan Taihe Hospital
Hubei
Ningxiang People's Hospital
Hunan
China-Japan Union Hospital of Jilin University
Jilin City
Linyi People's Hospital
Linyi, Shandong
Maoming People's Hospital
Maoming
Binzhou People's Hospital
Shandong
Shantou Central Hospital
Shantou, Guangdong
Shanxi People's Hospital
Shanxi, Taiyuan
The 4th Affiliated Hospital of CMU
Shenyang, Liaoning
Shunde Hospital of Southern Medical University
Shunde
Jingjiang People's Hospital
Taizhou
Tianjin TEDA Hospital
Tianjin
Wuhan Central Hospital
Wuhan, Hubei
Australia12 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Royal Brisbane & Women's Hospital
Brisbane, Queensland
Monash Medical Centre
Clayton, Victoria, 3168
Gold Coast University Hospital
Gold Coast, Queensland, 4215
Liverpool Hospital
Liverpool, New South Wales, 2170
Mobile Stroke Unit
Melbourne, Victoria, 3050
Royal Melbourne Hospital
Melbourne, Victoria
Fiona Stanley Hospital
Murdoch, Western Australia, 6150
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009
John Hunter Hospital
New Lambton, New South Wales, 2305
Royal North Shore Hospital
St Leonards, New South Wales, 2605
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Vietnam3 sites
Bach Mai Hospital
Hanoi
Military Hospital 103
Hanoi
115 People's Hospital
Ho Chi Minh City
About this study
Official title: DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With Endovascular Clot Retrieval Within 4.5 Hours of Stroke Onset
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
- Ischemic Stroke
- Being tested
- Direct endovascular clot retrieval, Bridging thrombolysis followed by ECR
- 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
- Medical subject headings
- Ischemic Stroke, Stroke, Ischemia, Cerebral Infarction, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Direct endovascular clot retrievalOther
Direct endovascular clot retrieval within 4.5 hours of stroke onset
Bridging thrombolysis followed by ECROther
Bridging thrombolysis followed by ECR within 4.5 hours of stroke onset
| Study group | Role | What they receive |
|---|---|---|
| Direct endovascular clot retrieval | Other | Endovascular clot retrieval (ECR) within 4.5 hours stroke Receives: Other: Direct endovascular clot retrieval |
| Bridging thrombolysis followed by ECR | Other | 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 Receives: Other: Bridging thrombolysis followed by ECR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Rankin Scale (mRS)- ordinal analysis
Modified Rankin Scale (mRS) 0-2 or no change from baseline
Measured: 3 months
Secondary outcomes (4)
modified Rankin Scale (mRS)- ordinal analysis
mRS 0-1 or no change from baseline
Measured: 3 months
Death
Death due to any cause
Measured: 3 months
Angiographic reperfusion
Proportion of patients with good angiographic reperfusion (mTICI 2b-3)
Measured: Baseline
Symptomatic intracranial haemorrhage (sICH)
Proportion of patients with sICH
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2018
- Study start27 Apr 2018
- Primary completion8 Sep 2021
- Study completion8 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomised to either direct endovascular clot retrieval or to bridging intravenous thrombolysis with endovascular clot retrieval.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 295 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuroscience Trials Australia
- Sponsor type
- University, hospital or other
- Collaborators
- The Florey Institute of Neuroscience and Mental Health
- Responsible party
- Sponsor
- Investigators
- Peter Mitchell, MD, Principal investigator, Melbourne HealthBernard Yan, MD, Principal investigator, Melbourne Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03494920
- Sponsor's protocol ID
- NTA1601
- Status last verified
- Jul 2021
- First submitted
- 4 Apr 2018
- Last updated
- 16 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
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 35810757Mitchell 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
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With Endovascular Clot Retrieval Within 4.5 Hours of Stroke Onset
- ClinicalTrials.gov ID
- NCT03494920
- Acronym / sponsor ID
- NTA1601
- Conditions
- Ischemic Stroke
- Keywords
- Stroke, Ischemia, Cerebral Infarction, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 295 participants (actual)
- Lead sponsor
- Neuroscience Trials AustraliaUniversity, hospital or other
- Collaborators
- The Florey Institute of Neuroscience and Mental Health
- Study start
- 27 Apr 2018 (actual)
- Primary completion
- 8 Sep 2021 (actual)
- Study completion
- 8 Sep 2021 (actual)
- First posted
- 11 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomised to either direct endovascular clot retrieval or to bridging intravenous thrombolysis with endovascular clot retrieval.
| Arm | Type | Receives |
|---|---|---|
| Direct endovascular clot retrieval | Other | Other: Direct endovascular clot retrievalEndovascular clot retrieval (ECR) within 4.5 hours stroke |
| Bridging thrombolysis followed by ECR | Other | Other: Bridging thrombolysis followed by ECRIntravenous 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Direct endovascular clot retrievalDirect endovascular clot retrieval within 4.5 hours of stroke onset | Other | Direct endovascular clot retrieval |
| Bridging thrombolysis followed by ECRBridging thrombolysis followed by ECR within 4.5 hours of stroke onset | Other | Bridging thrombolysis followed by ECR |
Primary outcome
Modified Rankin Scale (mRS)- ordinal analysis
Time frame: 3 months
Modified Rankin Scale (mRS) 0-2 or no change from baseline
4 secondary outcomes
modified Rankin Scale (mRS)- ordinal analysis
Time frame: 3 months
Death
Time frame: 3 months
Angiographic reperfusion
Time frame: Baseline
Symptomatic intracranial haemorrhage (sICH)
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2022.
- Derived from this study: PubMed 35810757Mitchell 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.
- Derived from this study: PubMed 35135060Mitchell 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Mitchell, MD principal investigator
Melbourne Health
Bernard Yan, MD principal investigator
Melbourne Health
33 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Direct endovascular clot retrieval and Bridging thrombolysis followed by ECR in people with Ischemic Stroke, run by Neuroscience Trials Australia at 33 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in China, Australia, Vietnam, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modified Rankin Scale (mRS)- ordinal analysis (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03494920, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2022.