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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02142283




Registration number
NCT02142283
Ethics application status
Date submitted
15/05/2014
Date registered
20/05/2014
Date last updated
20/07/2018

Titles & IDs
Public title
Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo
Scientific title
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)
Secondary ID [1] 0 0
T4024
Universal Trial Number (UTN)
Trial acronym
DAWN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischemic Stroke 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Trevo Thrombectomy Procedure
Other interventions - Medical Management

Experimental: Trevo Thrombectomy Procedure - Trevo Thrombectomy Procedure and Medical Management

Active Comparator: Medical Management - Medical Management


Treatment: Devices: Trevo Thrombectomy Procedure
stent retriever; intended to restore blood flow in the neurovasculature by removing thrombus (clot)

Other interventions: Medical Management
Standard of Care not including mechanical thrombectomy, no intra arterial treatment, may include aspirin, therapy etc

Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Weighted Modified Rankin Scale (mRS) Score, Lead Co-Primary Efficacy Outcome - 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
- no significant disability despite symptoms; able to carry out all usual duties and activities
- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
- moderate disability; requiring some help, but able to walk without assistance
- moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
- severe disability; bedridden, incontinent and requiring constant nursing care and attention
- dead
Timepoint [1] 0 0
90 days
Primary outcome [2] 0 0
Functional Independence (mRS 0-2), Nested Co-Primary Efficacy Outcome - 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
- no significant disability despite symptoms; able to carry out all usual duties and activities
- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
Timepoint [2] 0 0
90 days
Primary outcome [3] 0 0
Stroke-related Mortality, Primary Safety Outcome
Timepoint [3] 0 0
90 days
Secondary outcome [1] 0 0
Good Functional Outcome - 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
- no significant disability despite symptoms; able to carry out all usual duties and activities
- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
Timepoint [1] 0 0
90 days
Secondary outcome [2] 0 0
Early Response - 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.
Timepoint [2] 0 0
5-7 Days
Secondary outcome [3] 0 0
All Cause Mortality
Timepoint [3] 0 0
90 days
Secondary outcome [4] 0 0
Revascularization Rates - 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.
Timepoint [4] 0 0
24 hours
Secondary outcome [5] 0 0
Neurological Deterioration From Baseline NIHSS Score - 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.
Timepoint [5] 0 0
5-7 days

Eligibility
Key inclusion criteria
General

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

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Delaware
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
France
State/province [16] 0 0
Montpellier
Country [17] 0 0
France
State/province [17] 0 0
Toulouse
Country [18] 0 0
Spain
State/province [18] 0 0
Barcelona

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Stryker Neurovascular
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02142283
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tudor G Jovin, MD
Address 0 0
University of Pittsburg Medical Center Stroke Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications