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

Sponsor
Neuroscience Trials Australia (Other)
Overall Status
Completed
CT.gov ID
NCT03494920
Collaborator
The Florey Institute of Neuroscience and Mental Health (Other)
295
33
2
40.4
8.9
0.2

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
295 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.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 :
Apr 27, 2018
Actual Primary Completion Date :
Sep 8, 2021
Actual Study Completion Date :
Sep 8, 2021

Arms and Interventions

Arm Intervention/Treatment
Other: 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

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
Bridging thrombolysis followed by ECR within 4.5 hours of stroke onset

Outcome Measures

Primary Outcome Measures

  1. Modified Rankin Scale (mRS)- ordinal analysis [3 months]

    Modified Rankin Scale (mRS) 0-2 or no change from baseline

Secondary Outcome Measures

  1. modified Rankin Scale (mRS)- ordinal analysis [3 months]

    mRS 0-1 or no change from baseline

  2. Death [3 months]

    Death due to any cause

  3. Angiographic reperfusion [Baseline]

    Proportion of patients with good angiographic reperfusion (mTICI 2b-3)

  4. Symptomatic intracranial haemorrhage (sICH) [24 hours]

    Proportion of patients with sICH

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Liverpool Hospital Liverpool New South Wales Australia 2170
2 John Hunter Hospital New Lambton New South Wales Australia 2305
3 Royal North Shore Hospital St Leonards New South Wales Australia 2605
4 Royal Brisbane & Women's Hospital Brisbane Queensland Australia
5 Gold Coast University Hospital Gold Coast Queensland Australia 4215
6 Princess Alexandra Hospital Woolloongabba Queensland Australia 4102
7 Royal Adelaide Hospital Adelaide South Australia Australia 5000
8 Monash Medical Centre Clayton Victoria Australia 3168
9 Mobile Stroke Unit Melbourne Victoria Australia 3050
10 Royal Melbourne Hospital Melbourne Victoria Australia
11 Fiona Stanley Hospital Murdoch Western Australia Australia 6150
12 Sir Charles Gairdner Hospital Nedlands Western Australia Australia 6009
13 Shantou Central Hospital Shantou Guangdong China
14 Cangzhou Central Hospital Cangzhou Hebei China
15 Wuhan Central Hospital Wuhan Hubei China
16 The 4th Affiliated Hospital of CMU Shenyang Liaoning China
17 Linyi People's Hospital Linyi Shandong China
18 Shanxi People's Hospital Shanxi Taiyuan China
19 Beijing Fengtai Youanmen Hospital Beijing China
20 Beijing Tiantin Hospital Beijing China
21 Yunfu People's Hospital Guangdong China
22 Shiyan Taihe Hospital Hubei China
23 Ningxiang People's Hospital Hunan China
24 China-Japan Union Hospital of Jilin University Jilin China
25 Maoming People's Hospital Maoming China
26 Binzhou People's Hospital Shandong China
27 Shunde Hospital of Southern Medical University Shunde China
28 Jingjiang People's Hospital Taizhou China
29 Tianjin TEDA Hospital Tianjin China
30 Singapore General Hospital Singapore Singapore 169608
31 Bach Mai Hospital Hanoi Vietnam
32 Military Hospital 103 Hanoi Vietnam
33 115 People's Hospital Ho Chi Minh City Vietnam

Sponsors and Collaborators

  • Neuroscience Trials Australia
  • The Florey Institute of Neuroscience and Mental Health

Investigators

  • Principal Investigator: Peter Mitchell, MD, Melbourne Health
  • Principal Investigator: Bernard Yan, MD, Melbourne Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Neuroscience Trials Australia
ClinicalTrials.gov Identifier:
NCT03494920
Other Study ID Numbers:
  • NTA1601
First Posted:
Apr 11, 2018
Last Update Posted:
Jun 16, 2022
Last Verified:
Jul 1, 2021
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 16, 2022