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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02142283
Recruitment Status : Completed
First Posted : May 20, 2014
Results First Posted : July 20, 2018
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Stryker Neurovascular

Tracking Information
First Submitted Date  ICMJE May 15, 2014
First Posted Date  ICMJE May 20, 2014
Results First Submitted Date  ICMJE May 15, 2018
Results First Posted Date  ICMJE July 20, 2018
Last Update Posted Date July 20, 2018
Study Start Date  ICMJE July 2014
Actual Primary Completion Date May 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
  • Weighted Modified Rankin Scale (mRS) Score, Lead Co-Primary Efficacy Outcome [ Time Frame: 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 [ Time Frame: 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
  • Stroke-related Mortality, Primary Safety Outcome [ Time Frame: 90 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2014)
  • Weighted modified Rankin Scale (mRS) score [ Time Frame: 90 days ]
  • Stroke-related mortality [ Time Frame: 90 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
  • Good Functional Outcome [ Time Frame: 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
  • Early Response [ Time Frame: 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 [ Time Frame: 90 days ]
  • Revascularization Rates [ Time Frame: 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.
  • Neurological Deterioration From Baseline NIHSS Score [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2014)
  • Good functional outcome [ Time Frame: 90 days ]
    The proportion of subjects with a good functional outcome at 90 days, defined as mRS 0-2.
  • Early response [ Time Frame: 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.
  • All cause mortality [ Time Frame: 90 days ]
  • Median final infarct size [ Time Frame: 24 hours ]
    The median final infarct size at 24 hours from randomization, by MRI T2/Flair or CT.
  • Revascularization rates [ Time Frame: 24 hours ]
    Revascularization rates at 24 hours from randomization, by CT-MR core lab assessment of vessel patency on CTA/MRA.
  • Vessel reperfusion rates [ Time Frame: Immediately after device usage and at the end of the thrombectomy procedure ]
    Vessel reperfusion rates (percentages) post device and post procedure, by angiography core lab measurement of modified TICI ≥ 2b (Treatment arm only).
  • Symptomatic intracranial hemorrhage [ Time Frame: 24 hours ]
    Symptomatic intracranial hemorrhage, by ECASS III definition, within 24 hours post randomization.
  • Neurological deterioration from baseline NIHSS score [ Time Frame: 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.
  • Procedure-related and device-related SAEs [ Time Frame: 24 hours ]
    Procedure-related and device-related serious adverse events (SAEs) through 24 hours post randomization (Treatment arm only).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo
Official Title  ICMJE Diffusion Weighted Imaging (DWI) or Computerized Tomography Perfusion (CTP) Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention (DAWN)
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Ischemic Stroke
Intervention  ICMJE
  • Device: Trevo Thrombectomy Procedure
    stent retriever; intended to restore blood flow in the neurovasculature by removing thrombus (clot)
    Other Names:
    • Trevo ProVue Retriever
    • Trevo XP ProVue Retriever
  • Other: Medical Management
    Standard of Care not including mechanical thrombectomy, no intra arterial treatment, may include aspirin, therapy etc
    Other Name: Standard of Care
Study Arms  ICMJE
  • Experimental: Trevo Thrombectomy Procedure
    Trevo Thrombectomy Procedure and Medical Management
    Interventions:
    • Device: Trevo Thrombectomy Procedure
    • Other: Medical Management
  • Active Comparator: Medical Management
    Medical Management
    Intervention: Other: Medical Management
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 13, 2018)
206
Original Estimated Enrollment  ICMJE
 (submitted: May 19, 2014)
500
Actual Study Completion Date  ICMJE May 15, 2017
Actual Primary Completion Date May 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

General 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.)

Imaging Inclusion Criteria:

  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)

General 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

Imaging Exclusion Criteria:

  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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   France,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02142283
Other Study ID Numbers  ICMJE T4024
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Stryker Neurovascular
Study Sponsor  ICMJE Stryker Neurovascular
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tudor G Jovin, MD University of Pittsburg Medical Center Stroke Institute
Principal Investigator: Raul Nogueira, MD Marcus Stroke & Neuroscience Center, Grady Memorial Hospital
PRS Account Stryker Neurovascular
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP