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

NCT03494920 | Completed Phase 3 DMC

• 1 other identifier: NTA1601
• Study Type: interventional
• Target: 295
• Locations: 4 countries
• Sites: 33

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.

Conditions

Ischemic Stroke

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

Outcome Measures

Primary Outcomes (1)

• Modified Rankin Scale (mRS)- ordinal analysis

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

  3 months

Secondary Outcomes (4)

• modified Rankin Scale (mRS)- ordinal analysis

  3 months

• Death

  3 months

• Angiographic reperfusion

  Baseline

• Symptomatic intracranial haemorrhage (sICH)

  24 hours

Study Arms (2)

Direct endovascular clot retrieval

OTHER

Endovascular clot retrieval (ECR) within 4.5 hours stroke

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

Other: Bridging thrombolysis followed by ECR

Interventions

Direct endovascular clot retrieval OTHER

Direct endovascular clot retrieval within 4.5 hours of stroke onset

Direct endovascular clot retrieval

Bridging thrombolysis followed by ECR OTHER

Bridging thrombolysis followed by ECR within 4.5 hours of stroke onset

Bridging thrombolysis followed by ECR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Neuroscience Trials Australia: lead
• The Florey Institute of Neuroscience and Mental Health: collaborator

Study Sites (33)

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

John Hunter Hospital

New Lambton, New South Wales, 2305, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2605, Australia

Location

Royal Brisbane & Women's Hospital

Brisbane, Queensland, Australia

Location

Gold Coast University Hospital

Gold Coast, Queensland, 4215, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Mobile Stroke Unit

Melbourne, Victoria, 3050, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Shantou Central Hospital

Shantou, Guangdong, China

Location

Cangzhou Central Hospital

Cangzhou, Hebei, China

Location

Wuhan Central Hospital

Wuhan, Hubei, China

Location

The 4th Affiliated Hospital of CMU

Shenyang, Liaoning, China

Location

Linyi People's Hospital

Linyi, Shandong, China

Location

Shanxi People's Hospital

Shanxi, Taiyuan, China

Location

Beijing Fengtai Youanmen Hospital

Beijing, China

Location

Beijing Tiantin Hospital

Beijing, China

Location

Yunfu People's Hospital

Guangdong, China

Location

Shiyan Taihe Hospital

Hubei, China

Location

Ningxiang People's Hospital

Hunan, China

Location

China-Japan Union Hospital of Jilin University

Jilin, China

Location

Maoming People's Hospital

Maoming, China

Location

Binzhou People's Hospital

Shandong, China

Location

Shunde Hospital of Southern Medical University

Shunde, China

Location

Jingjiang People's Hospital

Taizhou, China

Location

Tianjin TEDA Hospital

Tianjin, China

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Bach Mai Hospital

Hanoi, Vietnam

Location

Military Hospital 103

Hanoi, Vietnam

Location

115 People's Hospital

Ho Chi Minh City, Vietnam

Location

Related Publications (2)

• 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.

  PMID: 35810757 DERIVED

• 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.

  PMID: 35135060 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; 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

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms; Infarction; Necrosis

Study Officials

• Peter Mitchell, MD

  Melbourne Health

  PRINCIPAL INVESTIGATOR

• Bernard Yan, MD

  Melbourne Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded core laboratory adjudications of the primary outcome. NIHSS and mRS (secondary outcomes) performed by blinded assessor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomised to either direct endovascular clot retrieval or to bridging intravenous thrombolysis with endovascular clot retrieval.

Study Record Dates

• First Submitted: April 4, 2018
• First Posted: April 11, 2018
• Study Start: April 27, 2018
• Primary Completion: September 8, 2021
• Study Completion: September 8, 2021
• Last Updated: June 16, 2022

Record last verified: 2021-07

Locations

CN (17); SG (1); VN (3); AU (12)