Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03494920
Recruitment Status : Recruiting
First Posted : April 11, 2018
Last Update Posted : October 30, 2019
Sponsor:
Collaborator:
The Florey Institute of Neuroscience and Mental Health
Information provided by (Responsible Party):
Neuroscience Trials Australia

Tracking Information
First Submitted Date  ICMJE April 4, 2018
First Posted Date  ICMJE April 11, 2018
Last Update Posted Date October 30, 2019
Actual Study Start Date  ICMJE April 27, 2018
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2018)
Modified Rankin Scale (mRS)- ordinal analysis [ Time Frame: 3 months ]
Modified Rankin Scale (mRS) 0-2 or no change from baseline
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2018)
  • modified Rankin Scale (mRS)- ordinal analysis [ Time Frame: 3 months ]
    mRS 0-1 or no change from baseline
  • Death [ Time Frame: 3 months ]
    Death due to any cause
  • Angiographic reperfusion [ Time Frame: Baseline ]
    Proportion of patients with good angiographic reperfusion (mTICI 2b-3)
  • Symptomatic intracranial haemorrhage (sICH) [ Time Frame: 24 hours ]
    Proportion of patients with sICH
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With Endovascular Clot Retrieval
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Ischemic Stroke
Intervention  ICMJE
  • Other: Direct endovascular clot retrieval
    Direct endovascular clot retrieval within 4.5 hours of stroke onset
  • Other: Bridging thrombolysis followed by ECR
    Bridging thrombolysis followed by ECR within 4.5 hours of stroke onset
Study Arms  ICMJE
  • Direct endovascular clot retrieval
    Endovascular clot retrieval (ECR) within 4.5 hours stroke
    Intervention: Other: Direct endovascular clot retrieval
  • 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
    Intervention: Other: Bridging thrombolysis followed by ECR
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 4, 2018)
780
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bernard Yan, MD 039349 2477 bernard.yan@mh.org.au
Contact: Michele Sallaberger 0438471423 michele.sallaberger@florey.edu.au
Listed Location Countries  ICMJE Australia,   China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03494920
Other Study ID Numbers  ICMJE NTA1601
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Neuroscience Trials Australia
Study Sponsor  ICMJE Neuroscience Trials Australia
Collaborators  ICMJE The Florey Institute of Neuroscience and Mental Health
Investigators  ICMJE
Principal Investigator: Peter Mitchell, MD Melbourne Health
Principal Investigator: Bernard Yan, MD Melbourne Health
PRS Account Neuroscience Trials Australia
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP