Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3)
|ClinicalTrials.gov Identifier: NCT02586415|
Recruitment Status : Terminated (Interim analysis showed a high likelihood of benefit in the endovascular group)
First Posted : October 26, 2015
Last Update Posted : November 14, 2017
|Condition or disease||Intervention/treatment||Phase|
|Stroke, Acute Cerebral Infarction||Procedure: Endovascular Thrombectomy Device: Trevo Retriever Device: Solitaire™ FR Revascularization Device Device: Penumbra thrombectomy system Device: Covidien MindFrame Capture Revascularization Device||Not Applicable|
DEFUSE 3 is a prospective randomized Phase III multicenter controlled trial of patients with acute ischemic anterior circulation strokes due to large artery occlusion treated between 6-16 hours of stroke onset with endovascular thrombectomy therapy vs. control.
The primary endpoint, the modified Rankin Score, will be assessed at 3 months. The patients' participation in the study concludes at that time (3 months from stroke onset). The study will randomize up to 476 patients over 4 years. The purpose of DEFUSE 3 is to assess the safety and efficacy of thrombectomy in carefully selected patients in an extended time window. Only the devices listed in this protocol will be used. Selection of the specific device (or devices) is determined by the individual endovascular therapist.
Patients who meet the inclusion criteria will undergo either CT Perfusion/CT Angiogram or MR DWI/PWI/MRA studies prior to randomization. Patients who have evidence of an ICA or MCA M1 occlusion and a Target Mismatch Profile will be randomized in a 1:1 ratio to treatment with one or more DEFUSE 3 approved thrombectomy devices (only the devices listed in this protocol are approved for use in DEFUSE 3) plus standard medical therapy versus standard medical therapy alone. Patients who are enrolled, but not randomized, will receive standard therapy according to local guidelines. Baseline data, and information about early stroke therapies, will be captured for this group of patients.
Randomization of a maximum of 476 patients is planned. A novel adaptive design will identify, at interim analyses, the group with the best prospect for showing benefit from endovascular treatment, based on baseline core lesion volumes and the times since stroke onset. Interim analyses will be conducted at 200 and 340 patients, at which time the study may stop for efficacy/futility, or the inclusion criteria may be adjusted in the case of futility.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||182 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3|
|Study Start Date :||April 2016|
|Actual Primary Completion Date :||August 23, 2017|
|Actual Study Completion Date :||August 23, 2017|
Active Comparator: endovascular thrombectomy therapy
Treatment with one or more thrombectomy devices (only the devices listed in this protocol are approved for use in DEFUSE 3) plus standard medical therapy for patients who have evidence of an ICA or MCA M1 occlusion and a Target Mismatch Profile.
Devices approved for use in DEFUSE 3:
Procedure: Endovascular Thrombectomy
Patients will be treated with thrombectomy devices (stent-retrievers) and/or suction thrombectomy systems currently cleared by the FDA for thrombus removal in patients experiencing an acute stroke following the published instructions for use for these devices. These devices will be used between 6 and 16 hours following symptom onset in DEFUSE 3 based on an FDA IDE. The devices which will be used are the Trevo Retriever, the Solitaire Revascularization Device and the Penumbra system thrombectomy system.Device: Trevo Retriever
Trevo Retriever is one of the interventional devices that is approved for use in DEFUSE 3 during the endovascular thrombectomy procedure. The device choice is at the discretion of the physician performing the procedure.Device: Solitaire™ FR Revascularization Device
Solitaire™ FR Revascularization Device is one of the interventional devices that is approved for use in DEFUSE 3 during the endovascular thrombectomy procedure. The device choice is at the discretion of the physician performing the procedure.Device: Penumbra thrombectomy system
Device: Covidien MindFrame Capture Revascularization Device
Penumbra thrombectomy system is one of the interventional devices that is approved for use in DEFUSE 3 during the endovascular thrombectomy procedure. The device choice is at the discretion of the physician performing the procedure. The Penumbra System includes:
• Penumbra Aspiration Pump (1115V) Penumbra System 054 Penumbra System MAX Penumbra System 110 Aspiration Tubing Penumbra System [026, 032, 041] Penumbra System Separator Flex [026, 032, 041, 054] Penumbra Pump MAX Penumbra System Reperfusion Catheter ACE64 & ACE68
Covidien MindFrame Capture Revascularization Device is one of the interventional devices that is approved for use in DEFUSE 3 during the endovascular thrombectomy procedure. The device choice is at the discretion of the physician performing the procedure.
No Intervention: Medical Management
standard medical therapy alone
- The distribution of scores on the modified Rankin Scale (mRS) at day 90 [ Time Frame: 90 days ]
The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. 0 - No symptoms.
- - No significant disability. Able to carry out all usual activities, despite some symptoms.
- - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
- - Moderate disability. Requires some help, but able to walk unassisted.
- - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
- - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
- - Dead.
- Functional Independence [ Time Frame: 90 days ]This outcome will look at the proportion of patients with mR S 0-2 at day 90 (indicating functional independence). The difference in the proportions of patients with mRS 0-2 between treatment arms will be assessed using logistic regression.
- Death (primary safety outcome) [ Time Frame: 90 days ]Death
- Symptomatic Intracranial Hemorrhage (primary safety outcome) [ Time Frame: 36 hours ]Defined as NIHSS worsening of 4 or more points associated with ICH within 36 hours of randomization
- Early neurological deterioration (Safety Outcome) [ Time Frame: 5 days ]Significant neurological deterioration prior to discharge (defined as an increase of 4 points or more on the NIHSS)
- Parenchymal hematoma type 2 (Safety Outcome) [ Time Frame: 24 hours ]PH 2 rates on the 24 hour scan
- Infarct Volume (Imaging Outcome) [ Time Frame: 24 hours ]Infarct volume on diffusion-weighted MRI (or CT if MRI not feasible) at 24 (±6) hours after randomization
- Lesion Growth (Imaging Outcome) [ Time Frame: 24 hours ]Lesion growth between the RAPID-identified ischemic core on baseline imaging and the infarct volume at 24 hours
- Reperfusion (Imaging Outcome) [ Time Frame: 24 hours ]Successful reperfusion defined as a >90% reduction in Tmax>6sec lesion volume between baseline and 24 hours
- Recanalization (Imaging Outcome) [ Time Frame: 24 hours ]Recanalization of the primary arterial occlusive lesion at 24-hours on CTA/MRA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02586415
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|Principal Investigator:||Gregory Albers, MD||Stanford University|
|Principal Investigator:||Michael Marks, MD||Stanford University|
|Principal Investigator:||Maarten Lansberg, MD, PhD||Stanford University|