Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo

NCT ID: NCT02142283

Last Updated: 2018-07-20

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

206 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-31

Study Completion Date

2017-05-15

Brief Summary

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The purpose of the study is to evaluate the hypothesis that Trevo thrombectomy plus medical management leads to superior clinical outcomes at 90 days as compared to medical management alone in appropriately selected subjects experiencing an acute ischemic stroke when treatment is initiated within 6-24 hours after last seen well.

Detailed Description

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The study is a prospective, randomized, multi-center, Phase II/III (feasibility/pivotal), adaptive, controlled trial, designed to demonstrate that mechanical thrombectomy using the Trevo Retriever with medical management is superior to medical management alone in improving clinical outcomes at 90 days in appropriately selected wake up and late presenting acute ischemic stroke subjects.

The intent of this study is to support the use of the Trevo Retriever beyond the currently labeled 8 hour indicated time limit in wake up, unclear onset, and late presenting ischemic stroke subjects, who currently have no other option besides medical management of their symptoms.

Patients with wake-up strokes, strokes with unclear onset time, and witnessed late presenting strokes may potentially benefit from intra-arterial reperfusion therapy. However, an important indicator of whether subjects will benefit or not during this later time window is the confirmation of a large vessel occlusion (LVO), and assessment of the core infarct volume relative to the volume of salvageable penumbra. Therefore, standardized imaging selection of subjects is required for inclusion into the study.

This trial has been designed with subject safety in mind, as a seamless Phase II (feasibility) / Phase III (pivotal) adaptive design, in order to address the concerns around potential unknown harms to enrolled subjects. This study will help to answer the question of whether carefully selecting subjects by using Clinical Imaging Mismatch will allow acute ischemic stroke patients who present at or beyond 6 hours from Time Last Seen Well (TLSW) to be considered for intra-arterial intervention. If Trevo thrombectomy plus medical management leads to better clinical outcomes over medical management alone, more patients in the future could receive endovascular treatment (either in addition to or in lieu of IV tPA).

Conditions

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Ischemic Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Trevo Thrombectomy Procedure

Trevo Thrombectomy Procedure and Medical Management

Group Type EXPERIMENTAL

Trevo Thrombectomy Procedure

Intervention Type DEVICE

stent retriever; intended to restore blood flow in the neurovasculature by removing thrombus (clot)

Medical Management

Intervention Type OTHER

Standard of Care not including mechanical thrombectomy, no intra arterial treatment, may include aspirin, therapy etc

Medical Management

Medical Management

Group Type ACTIVE_COMPARATOR

Medical Management

Intervention Type OTHER

Standard of Care not including mechanical thrombectomy, no intra arterial treatment, may include aspirin, therapy etc

Interventions

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Trevo Thrombectomy Procedure

stent retriever; intended to restore blood flow in the neurovasculature by removing thrombus (clot)

Intervention Type DEVICE

Medical Management

Standard of Care not including mechanical thrombectomy, no intra arterial treatment, may include aspirin, therapy etc

Intervention Type OTHER

Other Intervention Names

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Trevo ProVue Retriever Trevo XP ProVue Retriever Standard of Care

Eligibility Criteria

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Inclusion Criteria

1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, and subject belongs to one of the following subgroups:

1. Subject has failed IV t-PA therapy (defined as a confirmed persistent occlusion 60 min after administration)
2. Subject is contraindicated for IV t-PA administration
2. Age ≥18
3. Baseline NIHSS ≥10 (assessed within one hour of measuring core infarct volume)
4. Subject can be randomized between with 6 to 24 hours after time last known well
5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1)
6. Anticipated life expectancy of at least 6 months
7. Subject willing/able to return for protocol required follow up visits
8. Subject or subject's Legally Authorized Representative (LAR) has signed the study Informed Consent form\*

* If approved by local ethics committee and country regulations, the investigator is allowed to enroll a patient utilizing emergency informed consent procedures if neither the patient nor the representative or person of trust is available to sign the informed consent form. However, as soon as possible, the patient is informed and his/her consent is requested for the possible continuation of this research. (Not applicable to U.S. Sites.)


1. \< 1/3 MCA territory involved, as evidenced by CT or MRI
2. Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA
3. Clinical Imaging Mismatch (CIM) defined as one of the following on MR-DWI or CTP-rCBF maps:

1. 0-\<21 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old)
2. 0-\<31 cc core infarct and NIHSS ≥ 10 (and age \< 80 years old)
3. 31 cc to \<51 cc core infarct and NIHSS ≥ 20 (and age \< 80 years old)

Exclusion Criteria

1. History of severe head injury within past 90 days with residual neurological deficit, as determined by medical history
2. Rapid improvement in neurological status to an NIHSS \<10 or evidence of vessel recanalization prior to randomization
3. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor (e.g. Aricept)
4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment
5. Baseline blood glucose of \<50mg/dL (2.78 mmol) or \>400mg/dL (22.20 mmol)
6. Baseline hemoglobin counts of \<7 mmol/L
7. Baseline platelet count \< 50,000/uL
8. Abnormal baseline electrolyte parameters as defined by sodium concentration \<130 mmol/L, potassium concentration \<3 mEq/L or \>6 mEq/L
9. Renal failure as defined by a serum creatinine \>3.0 mg/dL (264 µmol/L) NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels
10. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR \> 3.0 or PTT \> 3 times normal. Patients on factor Xa inhibitor for 24-48 hours ago must have a normal PTT.
11. Any active or recent hemorrhage within the past 30 days
12. History of severe allergy (more than rash) to contrast medium
13. Severe, sustained hypertension (Systolic Blood Pressure \>185 mmHg or Diastolic Blood Pressure \>110 mmHg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using medication the subject can be enrolled
14. Female who is pregnant or lactating at time of admission
15. Current participation in another investigational drug or device study
16. Presumed septic embolus, or suspicion of bacterial endocarditis
17. Treatment with any cleared thrombectomy devices or other intra-arterial (neurovascular) therapies prior to randomization


1. Evidence of intracranial hemorrhage on CT/MRI
2. CTA or MRA evidence of flow limiting carotid dissection, high-grade stenosis, or complete cervical carotid occlusion requiring stenting at the time of the index procedure (i.e., mechanical thrombectomy).
3. Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude device delivery/deployment
4. Suspected cerebral vasculitis based on medical history and CTA/MRA
5. Suspected aortic dissection based on medical history and CTA/MRA
6. Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the Trevo device
7. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior circulation/vertebrobasilar system) as confirmed on CTA/MRA, or clinical evidence of bilateral strokes or strokes in multiple territories
8. Significant mass effect with midline shift as confirmed on CT/MRI
9. Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stryker Neurovascular

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tudor G Jovin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburg Medical Center Stroke Institute

Raul Nogueira, MD

Role: PRINCIPAL_INVESTIGATOR

Marcus Stroke & Neuroscience Center, Grady Memorial Hospital

Locations

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Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

Christiana Care

Newark, Delaware, United States

Site Status

Memorial Regional

Hollywood, Florida, United States

Site Status

Baptist Jacksonville

Jacksonville, Florida, United States

Site Status

Jackson Memorial/University of Miami

Miami, Florida, United States

Site Status

Florida Hospital; Neuroscience Research Center

Orlando, Florida, United States

Site Status

Emory University at Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status

Wellstar Kennestone Hospital

Marietta, Georgia, United States

Site Status

RUSH University Medical Center

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Baptist Health Lexington

Lexington, Kentucky, United States

Site Status

St. Joseph Mercy - Oakland

Pontiac, Michigan, United States

Site Status

JFK Neuroscience Institute at JFK Medical Center

Edison, New Jersey, United States

Site Status

Capital Health System

Trenton, New Jersey, United States

Site Status

Buffalo General Medical Center

Buffalo, New York, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

Riverside Methodist Hospital/ Ohio Health Research Institute

Columbus, Ohio, United States

Site Status

Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

UPMC Stroke Institute

Pittsburgh, Pennsylvania, United States

Site Status

Erlanger Health System

Chattanooga, Tennessee, United States

Site Status

Valley Baptist Medical Center-Harlingen

Harlingen, Texas, United States

Site Status

North Texas Stroke Center HCA (dba TSI)

Plano, Texas, United States

Site Status

Royal Melbourne

Parkville, , Australia

Site Status

Toronto Western Hospital - University Health Network

Toronto, Ontario, Canada

Site Status

Hôpital Gui de Chauliac

Montpellier, , France

Site Status

Hopital Purpan - Toulouse

Toulouse, , France

Site Status

Vall d'Hebron Barcelona

Barcelona, , Spain

Site Status

Hospital Clinic - Barcelona

Barcelona, , Spain

Site Status

Hospital Germans Trias I Pujol

Barcelona, , Spain

Site Status

Hospital Universitari de Bellvitge

Barcelona, , Spain

Site Status

Countries

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United States Australia Canada France Spain

References

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Roaldsen MB, Lindekleiv H, Mathiesen EB. Intravenous thrombolytic treatment and endovascular thrombectomy for ischaemic wake-up stroke. Cochrane Database Syst Rev. 2021 Dec 1;12(12):CD010995. doi: 10.1002/14651858.CD010995.pub3.

Reference Type DERIVED
PMID: 34850380 (View on PubMed)

Liebeskind DS, Saber H, Xiang B, Jadhav AP, Jovin TG, Haussen DC, Budzik RF, Bonafe A, Bhuva P, Yavagal DR, Hanel RA, Ribo M, Cognard C, Sila C, Hassan AE, Smith WS, Saver JL, Nogueira RG; DAWN Investigators. Collateral Circulation in Thrombectomy for Stroke After 6 to 24 Hours in the DAWN Trial. Stroke. 2022 Mar;53(3):742-748. doi: 10.1161/STROKEAHA.121.034471. Epub 2021 Nov 3.

Reference Type DERIVED
PMID: 34727737 (View on PubMed)

Liebeskind DS, Saber H, Bhuva P, Xiang B, Yoo AJ, Jadhav AP, Haussen DC, Budzik RF, Bonafe A, Yavagal DR, Hanel RA, Ribo M, Cognard C, Sila C, Hassan AE, Smith WS, Saver JL, Nogueira RG, Jovin TG. Serial ASPECTS in the DAWN Trial: Infarct Evolution and Clinical Impact. Stroke. 2021 Oct;52(10):3318-3324. doi: 10.1161/STROKEAHA.120.033477. Epub 2021 Jul 20.

Reference Type DERIVED
PMID: 34281376 (View on PubMed)

Tekle WG, Hassan AE, Jadhav AP, Haussen DC, Budzik RF, Bonafe A, Bhuva P, Yavagal DR, Hanel RA, Ribo M, Cognard C, Sila CA, Smith WS, Saver JL, Liebeskind DS, Shields R, Nogueira RG, Jovin TG; DAWN Trial Investigators. Impact of Periprocedural and Technical Factors and Patient Characteristics on Revascularization and Outcome in the DAWN Trial. Stroke. 2020 Jan;51(1):247-253. doi: 10.1161/STROKEAHA.119.026437. Epub 2019 Nov 20.

Reference Type DERIVED
PMID: 31744425 (View on PubMed)

Aghaebrahim A, Jadhav AP, Hanel R, Sauvageau E, Granja MF, Zhang Y, Haussen DC, Budzik RF, Bonafe A, Bhuva P, Ribo M, Cognard C, Sila C, Yavagal D, Hassan AE, Smith WS, Saver J, Liebeskind DS, Nogueira RG, Jovin TG; DAWN Investigators. Outcome in Direct Versus Transfer Patients in the DAWN Controlled Trial. Stroke. 2019 Aug;50(8):2163-2167. doi: 10.1161/STROKEAHA.119.025710. Epub 2019 Jul 15.

Reference Type DERIVED
PMID: 31303153 (View on PubMed)

Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG; DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4;378(1):11-21. doi: 10.1056/NEJMoa1706442. Epub 2017 Nov 11.

Reference Type DERIVED
PMID: 29129157 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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T4024

Identifier Type: -

Identifier Source: org_study_id

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