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

Ischemic Stroke Clinical Trial

— DAWN  

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02142283
• Other study ID #: T4024
• Status: Completed
• Phase: N/A
• Start date: July 2014
• Est. completion date: May 15, 2017

Study information

• Verified date: July 2018
• Source: Stryker Neurovascular
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: May 15, 2017
• Est. primary completion date: May 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke

Intervention

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

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Stryker Neurovascular

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	90 days
Primary	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	90 days
Primary	Stroke-related Mortality, Primary Safety Outcome		90 days
Secondary	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	90 days
Secondary	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.	5-7 Days
Secondary	All Cause Mortality		90 days
Secondary	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.	24 hours
Secondary	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.	5-7 days