Clinical trial NCT03494920: DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With Endovascular Clot Retrieval
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Neuroscience Trials Australia
Sponsor class: OTHER
Collaborators: name: The Florey Institute of Neuroscience and Mental Health
First posted: 2018-04-11
Enrollment: 295
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomised to either direct endovascular clot retrieval or to bridging intravenous thrombolysis with endovascular clot retrieval.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Modified Rankin Scale (mRS)- ordinal analysis
timeFrame: 3 months
Secondary outcomes:
measure: modified Rankin Scale (mRS)- ordinal analysis
timeFrame: 3 months
measure: Death
timeFrame: 3 months
measure: Angiographic reperfusion
timeFrame: Baseline
measure: Symptomatic intracranial haemorrhage (sICH)
timeFrame: 24 hours
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: Mobile Stroke Unit
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Shantou
country: China
facility: Shantou Central Hospital
state: Guangdong
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Wuhan
country: China
facility: Wuhan Central Hospital
state: Hubei
city: Shenyang
country: China
facility: The 4th Affiliated Hospital of CMU
state: Liaoning
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Shanxi
country: China
facility: Shanxi People's Hospital
state: Taiyuan
city: Beijing
country: China
facility: Beijing Fengtai Youanmen Hospital
city: Beijing
country: China
facility: Beijing Tiantin Hospital
city: Guangdong
country: China
facility: Yunfu People's Hospital
city: Hubei
country: China
facility: Shiyan Taihe Hospital
city: Hunan
country: China
facility: Ningxiang People's Hospital
city: Jilin
country: China
facility: China-Japan Union Hospital of Jilin University
city: Maoming
country: China
facility: Maoming People's Hospital
city: Shandong
country: China
facility: Binzhou People's Hospital
city: Shunde
country: China
facility: Shunde Hospital of Southern Medical University
city: Taizhou
country: China
facility: Jingjiang People's Hospital
city: Tianjin
country: China
facility: Tianjin TEDA Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Hanoi
country: Vietnam
facility: Bach Mai Hospital
city: Hanoi
country: Vietnam
facility: Military Hospital 103
city: Ho Chi Minh City
country: Vietnam
facility: 115 People's Hospital
Study officials:
affiliation: Melbourne Health
name: Peter Mitchell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne Health
name: Bernard Yan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.