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

Ischemic Stroke Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03494920
• Other study ID #: NTA1601
• Status: Completed
• Phase: Phase 3
• Start date: April 27, 2018
• Est. completion date: September 8, 2021

Study information

• Verified date: July 2021
• Source: Neuroscience Trials Australia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: September 8, 2021
• Est. primary completion date: September 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke

Intervention

Other:
• Direct endovascular clot retrieval
Direct endovascular clot retrieval within 4.5 hours of stroke onset
• Bridging thrombolysis followed by ECR
Bridging thrombolysis followed by ECR within 4.5 hours of stroke onset

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Brisbane & Women's Hospital	Brisbane	Queensland
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Gold Coast University Hospital	Gold Coast	Queensland
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Mobile Stroke Unit	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
China	Beijing Fengtai Youanmen Hospital	Beijing
China	Beijing Tiantin Hospital	Beijing
China	Cangzhou Central Hospital	Cangzhou	Hebei
China	Yunfu People's Hospital	Guangdong
China	Shiyan Taihe Hospital	Hubei
China	Ningxiang People's Hospital	Hunan
China	China-Japan Union Hospital of Jilin University	Jilin
China	Linyi People's Hospital	Linyi	Shandong
China	Maoming People's Hospital	Maoming
China	Binzhou People's Hospital	Shandong
China	Shantou Central Hospital	Shantou	Guangdong
China	Shanxi People's Hospital	Shanxi	Taiyuan
China	The 4th Affiliated Hospital of CMU	Shenyang	Liaoning
China	Shunde Hospital of Southern Medical University	Shunde
China	Jingjiang People's Hospital	Taizhou
China	Tianjin TEDA Hospital	Tianjin
China	Wuhan Central Hospital	Wuhan	Hubei
Singapore	Singapore General Hospital	Singapore
Vietnam	Bach Mai Hospital	Hanoi
Vietnam	Military Hospital 103	Hanoi
Vietnam	115 People's Hospital	Ho Chi Minh City

Sponsors (2)

Lead Sponsor	Collaborator
Neuroscience Trials Australia	The Florey Institute of Neuroscience and Mental Health

Countries where clinical trial is conducted

Australia,  China,  Singapore,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Rankin Scale (mRS)- ordinal analysis	Modified Rankin Scale (mRS) 0-2 or no change from baseline	3 months
Secondary	modified Rankin Scale (mRS)- ordinal analysis	mRS 0-1 or no change from baseline	3 months
Secondary	Death	Death due to any cause	3 months
Secondary	Angiographic reperfusion	Proportion of patients with good angiographic reperfusion (mTICI 2b-3)	Baseline
Secondary	Symptomatic intracranial haemorrhage (sICH)	Proportion of patients with sICH	24 hours