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

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ClinicalTrials.gov Identifier: NCT03494920
Recruitment Status : Recruiting
First Posted : April 11, 2018
Last Update Posted : July 29, 2019
Sponsor:
Collaborator:
The Florey Institute of Neuroscience and Mental Health
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Ischemic Stroke Other: Direct endovascular clot retrieval Other: Bridging thrombolysis followed by ECR Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 780 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be randomised to either direct endovascular clot retrieval or to bridging intravenous thrombolysis with endovascular clot retrieval.
Masking: Single (Outcomes Assessor)
Masking Description: Blinded core laboratory adjudications of the primary outcome. NIHSS and mRS (secondary outcomes) performed by blinded assessor.
Primary Purpose: Treatment
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
Actual Study Start Date : April 27, 2018
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : May 2021

Arm Intervention/treatment
Direct endovascular clot retrieval
Endovascular clot retrieval (ECR) within 4.5 hours stroke
Other: Direct endovascular clot retrieval
Direct endovascular clot retrieval within 4.5 hours of stroke onset

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
Bridging thrombolysis followed by ECR within 4.5 hours of stroke onset




Primary Outcome Measures :
  1. Modified Rankin Scale (mRS)- ordinal analysis [ Time Frame: 3 months ]
    Modified Rankin Scale (mRS) 0-2 or no change from baseline


Secondary Outcome Measures :
  1. modified Rankin Scale (mRS)- ordinal analysis [ Time Frame: 3 months ]
    mRS 0-1 or no change from baseline

  2. Death [ Time Frame: 3 months ]
    Death due to any cause

  3. Angiographic reperfusion [ Time Frame: Baseline ]
    Proportion of patients with good angiographic reperfusion (mTICI 2b-3)

  4. Symptomatic intracranial haemorrhage (sICH) [ Time Frame: 24 hours ]
    Proportion of patients with sICH



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03494920


Contacts
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Contact: Bernard Yan, MD 039349 2477 bernard.yan@mh.org.au
Contact: Michele Sallaberger 0438471423 michele.sallaberger@florey.edu.au

Locations
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Australia, New South Wales
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 2170
Principal Investigator: Alan McDougall         
John Hunter Hospital Recruiting
New Lambton, New South Wales, Australia, 2305
Principal Investigator: Ferdi Miteff         
Royal North Shore Hospital Recruiting
St Leonards, New South Wales, Australia, 2605
Contact: Martin Krause, A/Prof.         
Principal Investigator: Martin Krause, A/Prof.         
Australia, Queensland
Royal Brisbane & Women's Hospital Recruiting
Brisbane, Queensland, Australia
Principal Investigator: Andrew Wong         
Princess Alexandra Hospital Not yet recruiting
Woolloongabba, Queensland, Australia, 4102
Principal Investigator: Darshan Shah         
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Principal Investigator: Timothy Kleinig         
Australia, Victoria
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
Principal Investigator: Henry Ma         
Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia
Contact: Bernard Yan         
Principal Investigator: Bernard Yan         
Australia, Western Australia
Fiona Stanley Hospital Not yet recruiting
Murdoch, Western Australia, Australia, 6150
Principal Investigator: Darshan Ghia         
Sir Charles Gairdner Hospital Not yet recruiting
Nedlands, Western Australia, Australia, 6009
Principal Investigator: David Blacker         
China
Beijing Fengtai Youanmen Hospital Recruiting
Beijing, China
Principal Investigator: Shiyong Zhang         
Beijing Tiantin Hospital Recruiting
Beijing, China
Principal Investigator: Zhong Rong Miao         
Yunfu People's Hospital Recruiting
Guangdong, China
Principal Investigator: Zhilin Wu         
Shiyan Taihe Hospital Recruiting
Hubei, China
Principal Investigator: Zhibing Ai         
Binzhou People's Hospital Recruiting
Shandong, China
Principal Investigator: Guoqing Wang         
Shunde Hospital of Southern Medical University Active, not recruiting
Shunde, China
Jiingjiang People's Hospital Recruiting
Taizhou, China
Principal Investigator: Yan Liu         
Tianjin TEDA Hospital Recruiting
Tianjin, China
Principal Investigator: Zaiyu Guo         
Sponsors and Collaborators
Neuroscience Trials Australia
The Florey Institute of Neuroscience and Mental Health
Investigators
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Principal Investigator: Peter Mitchell, MD Melbourne Health
Principal Investigator: Bernard Yan, MD Melbourne Health

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Responsible Party: Neuroscience Trials Australia
ClinicalTrials.gov Identifier: NCT03494920     History of Changes
Other Study ID Numbers: NTA1601
First Posted: April 11, 2018    Key Record Dates
Last Update Posted: July 29, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Neuroscience Trials Australia:
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
Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Plasminogen
Molecular Mechanisms of Pharmacological Action
Fibrinolytic Agents
Fibrin Modulating Agents