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

Not Applicable

Completed

Conditions: Ischemic Stroke

Interventions: Device: Trevo Thrombectomy Procedure
Other: Medical Management

Registration Number: NCT02142283

Lead Sponsor: Stryker Neurovascular

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 206

Inclusion Criteria

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
Age ≥18
Baseline NIHSS ≥10 (assessed within one hour of measuring core infarct volume)
Subject can be randomized between with 6 to 24 hours after time last known well
No significant pre-stroke disability (pre-stroke mRS must be 0 or 1)
Anticipated life expectancy of at least 6 months
Subject willing/able to return for protocol required follow up visits
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.)

Imaging Inclusion Criteria:

< 1/3 MCA territory involved, as evidenced by CT or MRI
Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA
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)

General

Exclusion Criteria

History of severe head injury within past 90 days with residual neurological deficit, as determined by medical history
Rapid improvement in neurological status to an NIHSS <10 or evidence of vessel recanalization prior to randomization
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)
Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment
Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol)
Baseline hemoglobin counts of <7 mmol/L
Baseline platelet count < 50,000/uL
Abnormal baseline electrolyte parameters as defined by sodium concentration <130 mmol/L, potassium concentration <3 mEq/L or >6 mEq/L
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
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.
Any active or recent hemorrhage within the past 30 days
History of severe allergy (more than rash) to contrast medium
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
Female who is pregnant or lactating at time of admission
Current participation in another investigational drug or device study
Presumed septic embolus, or suspicion of bacterial endocarditis
Treatment with any cleared thrombectomy devices or other intra-arterial (neurovascular) therapies prior to randomization

Imaging Exclusion Criteria:

Evidence of intracranial hemorrhage on CT/MRI
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).
Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude device delivery/deployment
Suspected cerebral vasculitis based on medical history and CTA/MRA
Suspected aortic dissection based on medical history and CTA/MRA
Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the Trevo device
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
Significant mass effect with midline shift as confirmed on CT/MRI
Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Trevo Thrombectomy Procedure	Trevo Thrombectomy Procedure	Trevo Thrombectomy Procedure and Medical Management
Trevo Thrombectomy Procedure	Medical Management	Trevo Thrombectomy Procedure and Medical Management
Medical Management	Medical Management	Medical Management

Primary Outcome Measures

Name	Time	Method
Stroke-related Mortality, Primary Safety Outcome	90 days
Weighted Modified Rankin Scale (mRS) Score, Lead Co-Primary Efficacy Outcome	90 days	mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1. - no significant disability despite symptoms; able to carry out all usual duties and activities 2. - slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. - moderate disability; requiring some help, but able to walk without assistance 4. - moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. - severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. - dead
Functional Independence (mRS 0-2), Nested Co-Primary Efficacy Outcome	90 days	Number of participants with functional independence mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1. - no significant disability despite symptoms; able to carry out all usual duties and activities 2. - slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance

Secondary Outcome Measures

Name	Time	Method
Good Functional Outcome	90 days	Proportion of participants with functional independence mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes neurological disability. Functional Independence: 0 - no symptoms at all 1. - no significant disability despite symptoms; able to carry out all usual duties and activities 2. - slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
Revascularization Rates	24 hours	Revascularization rates at 24 hours from randomization are based on the assessment of vessel patency utilizing CTA/MRA and processed by the CT-MR core laboratory. Revascularization at 24 hours was defined as the presence of partial or complete recanalization. CTA/MRA images utilized ionizing radiation exposure.
Early Response	5-7 Days	The proportion of subjects with "early response" at Day 5-7/Discharge (whichever is earlier), defined as a National Institutes of Health Stroke Scale (NIHSS) drop of ≥10 from baseline or NIHSS score 0 or 1. The NIHSS is an assessment which objectively quantifies the impairment caused by a stroke. It is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
All Cause Mortality	90 days
Neurological Deterioration From Baseline NIHSS Score	5-7 days	Neurological deterioration from baseline NIHSS score through Day 5-7/discharge (whichever is earlier) post randomization. Neurological deterioration is defined as ≥ 4 point increase in the NIHSS score from the baseline score. The calculated difference in NIHSS scores was assessed at baseline and Day 5-7/discharge (two time points). The NIHSS is an assessment which objectively quantifies the impairment caused by a stroke. It is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.

Trial Locations

Locations (32): Baptist Health Lexington
🇺🇸
Lexington, Kentucky, United States
Buffalo General Medical Center
🇺🇸
Buffalo, New York, United States
UPMC Stroke Institute
🇺🇸
Pittsburgh, Pennsylvania, United States
Valley Baptist Medical Center-Harlingen
🇺🇸
Harlingen, Texas, United States
North Texas Stroke Center HCA (dba TSI)
🇺🇸
Plano, Texas, United States
Royal Melbourne
🇦🇺
Parkville, Australia
Vall d'Hebron Barcelona
🇪🇸
Barcelona, Spain
Hospital Clinic - Barcelona
🇪🇸
Barcelona, Spain
Hospital Germans Trias I Pujol
🇪🇸
Barcelona, Spain
Hospital Universitari de Bellvitge
🇪🇸
Barcelona, Spain
St. Joseph Mercy - Oakland
🇺🇸
Pontiac, Michigan, United States
Christiana Care
🇺🇸
Newark, Delaware, United States
Baptist Jacksonville
🇺🇸
Jacksonville, Florida, United States
JFK Neuroscience Institute at JFK Medical Center
🇺🇸
Edison, New Jersey, United States
Capital Health System
🇺🇸
Trenton, New Jersey, United States
Hôpital Gui de Chauliac
🇫🇷
Montpellier, France
Hopital Purpan - Toulouse
🇫🇷
Toulouse, France
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Riverside Methodist Hospital/ Ohio Health Research Institute
🇺🇸
Columbus, Ohio, United States
Erlanger Health System
🇺🇸
Chattanooga, Tennessee, United States
Memorial Regional
🇺🇸
Hollywood, Florida, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸
Los Angeles, California, United States
California Pacific Medical Center
🇺🇸
San Francisco, California, United States
Wellstar Kennestone Hospital
🇺🇸
Marietta, Georgia, United States
University of California, Los Angeles
🇺🇸
Los Angeles, California, United States
RUSH University Medical Center
🇺🇸
Chicago, Illinois, United States
Jackson Memorial/University of Miami
🇺🇸
Miami, Florida, United States
Emory University at Grady Memorial Hospital
🇺🇸
Atlanta, Georgia, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
Toronto Western Hospital - University Health Network
🇨🇦
Toronto, Ontario, Canada
Florida Hospital; Neuroscience Research Center
🇺🇸
Orlando, Florida, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States