Stroke, AcuteDEFUSE 3NCT02586415
Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3
A study testing Endovascular Thrombectomy, Trevo Retriever and Solitaire™ FR Revascularization Device in people with Stroke, Acute and Cerebral Infarction, run by Gregory W Albers at 40 sites in United States.
Trial summary
This is a study to evaluate the hypothesis that FDA cleared thrombectomy devices plus medical management leads to superior clinical outcomes in acute ischemic stroke patients at 90 days when compared to medical management alone in appropriately selected subjects with the Target mismatch profile and an MCA (M1 segment)… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Stroke, Acute, Cerebral Infarction
- What is being tested?
- Endovascular Thrombectomy, Trevo Retriever and Solitaire™ FR Revascularization Device
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 40 sitesUnited States
- Study dates
- Apr 2016to 23 Aug 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Clinical Inclusion Criteria:
- Signs \& symptoms consistent w/ the diagnosis of acute anterior circulation ischemic stroke
- Age 18-90 years
- Baseline NIHSSS is ≥ 6 and remains ≥6 immediately prior to randomization
- Endovascular treatment can be initiated (femoral puncture) between 6 and 16 hours of stroke onset. Stroke onset is defined as the time the patient was last known to be at their neurologic baseline (wake-up strokes are eligible if they meet the above time limits).
- modified Rankin Scale less than or equal to 2 prior to qualifying stroke (functionally independent for all ADLs)
- Patient/Legally Authorized Representative has signed the Informed Consent form.
Clinical Exclusion Criteria:
- Other serious, advanced, or terminal illness (investigator judgment) or life expectancy is less than 6 months.
- Pre-existing medical, neurological or psychiatric disease that would confound the neurological or functional evaluations
- Pregnant
- Unable to undergo a contrast brain perfusion scan with either MRI or CT
- Known allergy to iodine that precludes an endovascular procedure
- Treated with tPA >4.5 hours after time last known well
- Treated with tPA 3-4.5 hours after last known well AND any of the following; age >80, current anticoagulant use, history of diabetes or prior stroke, NIHSS >25
- Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR > 3 (recent use of one of the new oral anticoagulants is not an exclusion if estimated GFR > 30 ml/min).
- Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
- Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol)
- Baseline platelet count < 50,000/uL
- Severe, sustained hypertension (Systolic BP >185 mmHg or Diastolic BP >110 mmHg)
- Current participation in another investigational drug or device study
- Presumed septic embolus; suspicion of bacterial endocarditis
- Clot retrieval attempted using a neurothrombectomy device prior to 6 hrs from symptom onset
- Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the subject if an endovascular procedure was performed.
Neuroimaging Inclusion Criteria:
- ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA or CTA AND
- Target Mismatch Profile on CT perfusion or MRI (ischemic core volume is < 70 ml, mismatch ratio is >/= 1.8 and mismatch volume* is >/= 15 ml)
Alternative neuroimaging inclusion criteria (if perfusion imaging or CTA/MRA is technically inadequate):
- If CTA (or MRA) is technically inadequate:
Tmax>6s perfusion deficit consistent with an ICA or MCA-M1 occlusion AND Target Mismatch Profile (ischemic core volume is < 70 ml, mismatch ratio is >1.8 and mismatch volume is >15 ml as determined by RAPID software)
- If MRP is technically inadequate:
ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA (or CTA, if MRA is technically inadequate and a CTA was performed within 60 minutes prior to the MRI) AND DWI lesion volume < 25 ml
- If CTP is technically inadequate:
Patient can be screened with MRI and randomized if neuroimaging criteria are met.
Neuroimaging Exclusion Criteria:
- ASPECTS score <6 on non-contrast CT (if patient is enrolled based on CT perfusion criteria)
- Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
- Significant mass effect with midline shift
- Evidence of internal carotid artery dissection that is flow limiting or aortic dissection
- Intracranial stent implanted in the same vascular territory that precludes the safe deployment/removal of the neurothrombectomy device
- Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion).
Trial locations and contacts
40 sites in 1 country.
40 sites in 1 country
United States40 sites
University of Michigan Hospital
Ann Arbor, Michigan, 48109-5000
University Medical Center Brackenridge
Austin, Texas, 78701-1930
Seton Medical Center/UT Southwestern
Austin, Texas, 78705-1006
University of Alabama
Birmingham, Alabama, 35233-1932
Massachusetts General Hospital
Boston, Massachusetts, 02114-2621
The Brigham and Women's Hospital
Boston, Massachusetts, 02115-6110
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215-5400
Northwestern Memorial Hospital
Chicago, Illinois, 60611-2908
University of Cincinnati
Cincinnati, Ohio, 45221-0222
Cleveland Clinic
Cleveland, Ohio, 44195-0001
Palmetto Health Richland
Columbia, South Carolina, 29203-6863
Ohio State University Wexner Medical Center
Columbus, Ohio, 43210-1280
Community Regional Medical Center
Fresno, California, 93721-1324
Memorial Hermann Texas Medical Center
Houston, Texas, 77030-5401
University of Iowa Hospital and Clinics
Iowa City, Iowa, 52242-1009
Scripps Memorial Hospital
La Jolla, California, 92037-1205
UCSD Medical Center/Hillcrest Hospital
La Jolla, California, 92093
Keck Hospital of University of Southern California
Los Angeles, California, 90033-5313
University of Wisconsin
Madison, Wisconsin, 53715-1218
Abbott Northwestern Hospital
Minneapolis, Minnesota, 55407-3723
Hennepin County Medical Center
Minneapolis, Minnesota, 55415-1623
University of Minnesota Medical Center, Fairview
Minneapolis, Minnesota, 55455-0363
Vanderbilt University
Nashville, Tennessee, 37240-0001
Mount Sinai Hospital
New York, New York, 10029-6504
New York Presbyterian Hospital at Columbia
New York, New York, 10032-3725
NYP Weill Cornell Medical Center
New York, New York, 10065-4870
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104-4238
Temple University Hospital
Philadelphia, Pennsylvania, 19140-5103
Providence St. Vincent Medical Center
Portland, Oregon, 97225-6603
Oregon Health & Science University Hospital
Portland, Oregon, 97239-3098
Rhode Island Hospital
Providence, Rhode Island, 02903-4923
The Valley Hospital
Ridgewood, New Jersey, 07450
Intermountain Medical Center
Salt Lake City, Utah, 84111-1470
University of Utah Healthcare
Salt Lake City, Utah, 84112-9023
UCSF Medical Center, San Francisco, CA
San Francisco, California, 94110-3518
Harborview Medical Center
Seattle, Washington, 98104-2420
Stanford University
Stanford, California, 94305
Mercy Health St. Vincent Medical Center
Toledo, Ohio, 43608-2603
John Muir Medical Center
Walnut Creek, California, 94598-3122
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010-3017
About this study
This is a study to evaluate the hypothesis that FDA cleared thrombectomy devices plus medical management leads to superior clinical outcomes in acute ischemic stroke patients at 90 days when compared to medical management alone in appropriately selected subjects with the Target mismatch profile and an MCA (M1 segment) or ICA occlusion who can be randomized and have endovascular treatment initiated between 6-16 hours after last seen well.
Read the detailed description
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.
- Conditions
- Stroke, Acute, Cerebral Infarction
- Being tested
- Endovascular Thrombectomy, Trevo Retriever, Solitaire™ FR Revascularization Device, Penumbra thrombectomy system, Covidien MindFrame Capture Revascularization Device
- Keywords
- endovascular, endovascular procedure, Mechanical Thrombectomy
- Medical subject headings
- Stroke, Cerebral Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endovascular ThrombectomyProcedure or surgery
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.
Trevo RetrieverDevice
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.
Solitaire™ FR Revascularization DeviceDevice
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.
Penumbra thrombectomy systemDevice
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 DeviceDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| endovascular thrombectomy therapy | Active comparator | 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:
* Trevo Retriever
* Solitaire™ FR Revascularization Device
* Penumbra thrombectomy system
* Covidien MindFrame Capture Revascularization Device Receives: Procedure: Endovascular Thrombectomy; Device: Trevo Retriever; Device: Solitaire™ FR Revascularization Device; Device: Penumbra thrombectomy system; Device: Covidien MindFrame Capture Revascularization Device |
| Medical Management | No intervention | standard medical therapy alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Distribution of Scores on the Modified Rankin Scale (mRS) at Day 90
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.
Measured: Day 90
Secondary outcomes (1)
Count of Patients With mRS 0-2 at Day 90 as a Measure of Functional Independence
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.
Measured: day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2015 (estimated)
- Study startApr 2016
- Primary completion23 Aug 2017
- Study completion23 Aug 2017
Why it stopped: Interim analysis showed a high likelihood of benefit in the endovascular group
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Stroke, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 182 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gregory W Albers
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), University of Cincinnati, Medical University of South Carolina, NINDS Stroke Trials Network (StrokeNet)
- Responsible party
- Sponsor-investigator, Gregory W Albers, Stanford University
- Investigators
- Gregory Albers, MD, Principal investigator, Stanford UniversityMichael Marks, MD, Principal investigator, Stanford UniversityMaarten Lansberg, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02586415
- Sponsor's protocol ID
- 116661
- Other IDs
- U10NS086487, U01NS092076
- Acronym
- DEFUSE 3
- Status last verified
- May 2019
- First submitted
- 21 Oct 2015
- Last updated
- 21 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
Publications
Albers GW, Lansberg MG, Kemp S, Tsai JP, Lavori P, Christensen S, Mlynash M, Kim S, Hamilton S, Yeatts SD, Palesch Y, Bammer R, Broderick J, Marks MP. A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3). Int J Stroke. 2017 Oct;12(8):896-905. doi: 10.1177/1747493017701147. Epub 2017 Mar 24.
PubMed 28946832Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG; DEFUSE 3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Feb 22;378(8):708-718. doi: 10.1056/NEJMoa1713973. Epub 2018 Jan 24.
PubMed 29364767Marks MP, Heit JJ, Lansberg MG, Kemp S, Christensen S, Derdeyn CP, Rasmussen PA, Zaidat OO, Broderick JP, Yeatts SD, Hamilton S, Mlynash M, Albers GW; DEFUSE 3 Investigators. Endovascular Treatment in the DEFUSE 3 Study. Stroke. 2018 Aug;49(8):2000-2003. doi: 10.1161/STROKEAHA.118.022147.
PubMed 29986935Yu Y, Christensen S, Ouyang J, Scalzo F, Liebeskind DS, Lansberg MG, Albers GW, Zaharchuk G. Predicting Hypoperfusion Lesion and Target Mismatch in Stroke from Diffusion-weighted MRI Using Deep Learning. Radiology. 2023 Apr;307(1):e220882. doi: 10.1148/radiol.220882. Epub 2022 Dec 6.
PubMed 36472536Tate WJ, Polding LC, Christensen S, Mlynash M, Kemp S, Heit JJ, Marks MP, Albers GW, Lansberg MG. Predictors of Early and Late Infarct Growth in DEFUSE 3. Front Neurol. 2021 Jul 1;12:699153. doi: 10.3389/fneur.2021.699153. eCollection 2021.
PubMed 34276547Polding LC, Tate WJ, Mlynash M, Marks MP, Heit JJ, Christensen S, Kemp S, Albers GW, Lansberg MG; DEFUSE 3 Investigators. Quality of Life in Physical, Social, and Cognitive Domains Improves With Endovascular Therapy in the DEFUSE 3 Trial. Stroke. 2021 Apr;52(4):1185-1191. doi: 10.1161/STROKEAHA.120.031490. Epub 2021 Feb 18.
PubMed 33596675Sarraj A, Mlynash M, Heit J, Pujara D, Lansberg M, Marks M, Albers GW. Clinical Outcomes and Identification of Patients With Persistent Penumbral Profiles Beyond 24 Hours From Last Known Well: Analysis From DEFUSE 3. Stroke. 2021 Mar;52(3):838-849. doi: 10.1161/STROKEAHA.120.031147. Epub 2021 Feb 10.
PubMed 33563012Cereda CW, Mlynash M, Cippa PE, Kemp S, Heit JJ, Marks MP, Lansberg MG, Albers GW. Renal Safety of Multimodal Brain Imaging Followed by Endovascular Therapy. Stroke. 2021 Jan;52(1):313-316. doi: 10.1161/STROKEAHA.120.030816. Epub 2020 Nov 30.
PubMed 33250038Heit JJ, Mlynash M, Christensen S, Kemp SM, Lansberg MG, Marks MP, Olivot JM, Gregory AW. What predicts poor outcome after successful thrombectomy in late time windows? J Neurointerv Surg. 2021 May;13(5):421-425. doi: 10.1136/neurintsurg-2020-016125. Epub 2020 Jun 17.
PubMed 32554693Kim-Tenser M, Mlynash M, Lansberg MG, Tenser M, Bulic S, Jagadeesan B, Christensen S, Simpkins A, Albers GW, Marks MP, Heit JJ. CT perfusion core and ASPECT score prediction of outcomes in DEFUSE 3. Int J Stroke. 2021 Apr;16(3):288-294. doi: 10.1177/1747493020915141. Epub 2020 Mar 31.
PubMed 32233746Dula AN, Mlynash M, Zuck ND, Albers GW, Warach SJ; DEFUSE 3 Investigators. Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort. Stroke. 2020 Feb;51(2):481-488. doi: 10.1161/STROKEAHA.119.028205. Epub 2019 Dec 12.
PubMed 31826731Amukotuwa SA, Fischbein NJ, Albers GW, Davis S, Donnan GA, Andre JB, Bammer R. Comparison of T2*GRE and DSC-PWI for hemorrhage detection in acute ischemic stroke patients: Pooled analysis of the EPITHET, DEFUSE 2, and SENSE 3 stroke studies. Int J Stroke. 2020 Feb;15(2):216-225. doi: 10.1177/1747493019858781. Epub 2019 Jul 10.
PubMed 31291850Tate WJ, Polding LC, Kemp S, Mlynash M, Heit JJ, Marks MP, Albers GW, Lansberg MG. Thrombectomy Results in Reduced Hospital Stay, More Home-Time, and More Favorable Living Situations in DEFUSE 3. Stroke. 2019 Sep;50(9):2578-2581. doi: 10.1161/STROKEAHA.119.025165. Epub 2019 Jul 10.
PubMed 31288666Heit JJ, Mlynash M, Kemp SM, Lansberg MG, Christensen S, Marks MP, Ortega-Gutierrez S, Albers GW. Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study. Stroke. 2019 May;50(5):1172-1177. doi: 10.1161/STROKEAHA.119.024928.
PubMed 30932783Christensen S, Mlynash M, Kemp S, Yennu A, Heit JJ, Marks MP, Lansberg MG, Albers GW. Persistent Target Mismatch Profile >24 Hours After Stroke Onset in DEFUSE 3. Stroke. 2019 Mar;50(3):754-757. doi: 10.1161/STROKEAHA.118.023392.
PubMed 30735466
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3
- ClinicalTrials.gov ID
- NCT02586415
- Acronym / sponsor ID
- DEFUSE 3 / 116661
- Conditions
- Stroke, Acute, Cerebral Infarction
- Keywords
- endovascular, endovascular procedure, Mechanical Thrombectomy
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim analysis showed a high likelihood of benefit in the endovascular group
- Enrolment
- 182 participants (actual)
- Lead sponsor
- Gregory W AlbersUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), University of Cincinnati, Medical University of South Carolina, NINDS Stroke Trials Network (StrokeNet)
- Study start
- Apr 2016
- Primary completion
- 23 Aug 2017 (actual)
- Study completion
- 23 Aug 2017 (actual)
- First posted
- 26 Oct 2015 (estimated)
- Results
- Posted 19 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to evaluate the hypothesis that FDA cleared thrombectomy devices plus medical management leads to superior clinical outcomes in acute ischemic stroke patients at 90 days when compared to medical management alone in appropriately selected subjects with the Target mismatch profile and an MCA (M1 segment) or ICA occlusion who can be randomized and have endovascular treatment initiated between 6-16 hours after last seen well.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| endovascular thrombectomy therapy | Active comparator | Procedure: Endovascular Thrombectomy, Device: Trevo Retriever, Device: Solitaire™ FR Revascularization Device, Device: Penumbra thrombectomy system, Device: Covidien MindFrame Capture Revascularization DeviceTreatment 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: * Trevo Retriever * Solitaire™ FR Revascularization Device * Penumbra thrombectomy system * Covidien MindFrame Capture Revascularization Device |
| Medical Management | No intervention | –standard medical therapy alone |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endovascular ThrombectomyPatients 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. | Procedure or surgery | endovascular thrombectomy therapy |
| Trevo RetrieverTrevo 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 | endovascular thrombectomy therapy |
| Solitaire™ FR Revascularization DeviceSolitaire™ 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 | endovascular thrombectomy therapy |
| Penumbra thrombectomy systemPenumbra 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 | Device | endovascular thrombectomy therapy |
| Covidien MindFrame Capture Revascularization DeviceCovidien 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. | Device | endovascular thrombectomy therapy |
Primary outcome
The Distribution of Scores on the Modified Rankin Scale (mRS) at Day 90
Time frame: Day 90
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. 1. - No significant disability. Able to carry out all usual activities, despite some symptoms. 2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3. - Moderate disability. Requires some help, but able to walk unassisted. 4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6. - Dead.
1 secondary outcome
Count of Patients With mRS 0-2 at Day 90 as a Measure of Functional Independence
Time frame: day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28946832Albers GW, Lansberg MG, Kemp S, Tsai JP, Lavori P, Christensen S, Mlynash M, Kim S, Hamilton S, Yeatts SD, Palesch Y, Bammer R, Broderick J, Marks MP. A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3). Int J Stroke. 2017 Oct;12(8):896-905. doi: 10.1177/1747493017701147. Epub 2017 Mar 24.
- Results publication: PubMed 29364767Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG; DEFUSE 3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Feb 22;378(8):708-718. doi: 10.1056/NEJMoa1713973. Epub 2018 Jan 24.
- Results publication: PubMed 29986935Marks MP, Heit JJ, Lansberg MG, Kemp S, Christensen S, Derdeyn CP, Rasmussen PA, Zaidat OO, Broderick JP, Yeatts SD, Hamilton S, Mlynash M, Albers GW; DEFUSE 3 Investigators. Endovascular Treatment in the DEFUSE 3 Study. Stroke. 2018 Aug;49(8):2000-2003. doi: 10.1161/STROKEAHA.118.022147.
- Derived from this study: PubMed 36472536Yu Y, Christensen S, Ouyang J, Scalzo F, Liebeskind DS, Lansberg MG, Albers GW, Zaharchuk G. Predicting Hypoperfusion Lesion and Target Mismatch in Stroke from Diffusion-weighted MRI Using Deep Learning. Radiology. 2023 Apr;307(1):e220882. doi: 10.1148/radiol.220882. Epub 2022 Dec 6.
- Derived from this study: PubMed 34276547Tate WJ, Polding LC, Christensen S, Mlynash M, Kemp S, Heit JJ, Marks MP, Albers GW, Lansberg MG. Predictors of Early and Late Infarct Growth in DEFUSE 3. Front Neurol. 2021 Jul 1;12:699153. doi: 10.3389/fneur.2021.699153. eCollection 2021.
- Derived from this study: PubMed 33596675Polding LC, Tate WJ, Mlynash M, Marks MP, Heit JJ, Christensen S, Kemp S, Albers GW, Lansberg MG; DEFUSE 3 Investigators. Quality of Life in Physical, Social, and Cognitive Domains Improves With Endovascular Therapy in the DEFUSE 3 Trial. Stroke. 2021 Apr;52(4):1185-1191. doi: 10.1161/STROKEAHA.120.031490. Epub 2021 Feb 18.
- Derived from this study: PubMed 33563012Sarraj A, Mlynash M, Heit J, Pujara D, Lansberg M, Marks M, Albers GW. Clinical Outcomes and Identification of Patients With Persistent Penumbral Profiles Beyond 24 Hours From Last Known Well: Analysis From DEFUSE 3. Stroke. 2021 Mar;52(3):838-849. doi: 10.1161/STROKEAHA.120.031147. Epub 2021 Feb 10.
- Derived from this study: PubMed 33250038Cereda CW, Mlynash M, Cippa PE, Kemp S, Heit JJ, Marks MP, Lansberg MG, Albers GW. Renal Safety of Multimodal Brain Imaging Followed by Endovascular Therapy. Stroke. 2021 Jan;52(1):313-316. doi: 10.1161/STROKEAHA.120.030816. Epub 2020 Nov 30.
- Derived from this study: PubMed 32554693Heit JJ, Mlynash M, Christensen S, Kemp SM, Lansberg MG, Marks MP, Olivot JM, Gregory AW. What predicts poor outcome after successful thrombectomy in late time windows? J Neurointerv Surg. 2021 May;13(5):421-425. doi: 10.1136/neurintsurg-2020-016125. Epub 2020 Jun 17.
- Derived from this study: PubMed 32233746Kim-Tenser M, Mlynash M, Lansberg MG, Tenser M, Bulic S, Jagadeesan B, Christensen S, Simpkins A, Albers GW, Marks MP, Heit JJ. CT perfusion core and ASPECT score prediction of outcomes in DEFUSE 3. Int J Stroke. 2021 Apr;16(3):288-294. doi: 10.1177/1747493020915141. Epub 2020 Mar 31.
- Derived from this study: PubMed 31826731Dula AN, Mlynash M, Zuck ND, Albers GW, Warach SJ; DEFUSE 3 Investigators. Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort. Stroke. 2020 Feb;51(2):481-488. doi: 10.1161/STROKEAHA.119.028205. Epub 2019 Dec 12.
- Derived from this study: PubMed 31291850Amukotuwa SA, Fischbein NJ, Albers GW, Davis S, Donnan GA, Andre JB, Bammer R. Comparison of T2*GRE and DSC-PWI for hemorrhage detection in acute ischemic stroke patients: Pooled analysis of the EPITHET, DEFUSE 2, and SENSE 3 stroke studies. Int J Stroke. 2020 Feb;15(2):216-225. doi: 10.1177/1747493019858781. Epub 2019 Jul 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory Albers, MD principal investigator
Stanford University
Michael Marks, MD principal investigator
Stanford University
Maarten Lansberg, MD, PhD principal investigator
Stanford University
40 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Endovascular Thrombectomy, Trevo Retriever and Solitaire™ FR Revascularization Device in people with Stroke, Acute and Cerebral Infarction, run by Gregory W Albers at 40 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Distribution of Scores on the Modified Rankin Scale (mRS) at Day 90 (time frame: Day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02586415, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2019.