StrokeNet cIRB Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3)

Principal Investigator: Adam  DeHavenon
Keywords: Ischemic stroke , Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke , randomized, multi-center, phase II, adaptive, blinded endpoint controlled trial , Medical management alone Department: Neurology
IRB Number: 00089368 Co Investigator:  
Specialty: Radiology/Interventional, Neurology, Neurology, Neurology
Sub Specialties: Neurointerventional Radiology, Neuroimaging, Neuro Critical Care, Stroke
Recruitment Status: Recruiting

Contact Information

Kinga Aitken
kinga.aitken@hsc.utah.edu
801-581-5523

Brief Summary

DEFUSE 3 is a prospective randomized Phase III multicenter controlled trial of patients with acute ischemic anterior circulation strokes due to large artery occlusion treated between 6-16 hours of stroke onset with endovascular thrombectomy therapy vs. control.

 

The primary endpoint, the modified Rankin Scale, will be assessed at 3 months. The patients’ participation in the study concludes at that time (3 months from stroke onset).

The purpose of DEFUSE 3 is to assess the safety and efficacy of thrombectomy in carefully selected patients in an extended time window. Only the devices listed in this protocol will be used. Selection of the specific device (or devices) is determined by the individual endovascular therapist.

Inclusion Criteria

Clinical Inclusion Criteria:
1. Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke
2. Age 18-90 years
3. Baseline NIHSSS is ≥ 6 and remains ≥6 immediately prior to randomization
4. Endovascular treatment can be initiated (femoral puncture) between 6 and 16 hours of stroke onset. Stroke onset is defined as the time the patient was last known to be at their neurologic baseline (wake-up strokes are eligible if they meet the above time limits).
5. modified Rankin Scale less than or equal to 2 prior to qualifying stroke (functionally independent for all ADLs)
6. Patient/Legally Authorized Representative has signed the Informed Consent form.
 
Neuroimaging Inclusion Criteria:
1. ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA or CTA
AND
2. Target Mismatch Profile on CT perfusion or MRI (ischemic core volume is < 70 ml, mismatch ratio is > 1.8 and mismatch volume* is > 15 ml)
 
Alternative neuroimaging inclusion criteria (if perfusion imaging or CTA/MRA is technically inadequate):
A) If CTA (or MRA) is technically inadequate:
Tmax>6s perfusion deficit consistent with an ICA or MCA-M1 occlusion
AND
Target Mismatch Profile (ischemic core volume is < 70 ml, mismatch ratio is >1.8 and mismatch volume is >15 ml as determined by RAPID software)
B) If MRP is technically inadequate:
ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA (or CTA, if MRA is technically inadequate and a CTA was performed within 60 minutes prior to the MRI)
AND
DWI lesion volume < 25 ml
C) If CTP is technically inadequate:
Patient can be screened with MRI and randomized if neuroimaging criteria are met.

Exclusion Criteria

Clinical Exclusion Criteria:
1. Other serious, advanced, or terminal illness (investigator judgment) or life expectancy is less than 6 months.
2. Pre-existing medical, neurological or psychiatric disease that would confound the neurological or functional evaluations
3. Pregnant
4. Unable to undergo a contrast brain perfusion scan with either MRI or CT
5. Known allergy to iodine that precludes an endovascular proceedure
6. Treated with tPA >4.5 hours after time last known well
7. Treated with tPA 3-4.5 hours after last known well AND any of the following; age >80, current anticoagulant use, history of diabetes or prior stroke, NIHSS >25
8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR > 3 (recent use of one of the new oral anticoagulants is not an exclusion if estimated GFR > 30 ml/min).
9. Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
10. Baseline blood glucose of <50mg/dL (2.78 mmol) or >400mg/dL (22.20 mmol)
11. Baseline platelet count < 50,000/uL
12. Severe, sustained hypertension (Systolic Blood Pressure >185 mmHg or Diastolic Blood Pressure >110 mmHg)
13. Current participation in another investigational drug or device study
14. Presumed septic embolus; suspicion of bacterial endocarditis
15. Clot retrieval attempted using a neurothrombectomy device prior to 6 hours from symptom onset
 
 
 
 
Neuroimaging Exclusion Criteria:
1. ASPECTS score <6 on non-contrast CT (if baseline non-contrast CT was performed)
2. Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
3. Significant mass effect with midline shift
4. Evidence of internal carotid artery dissection that is flow limiting or aortic dissection
5. Intracranial stent implanted in the same vascular territory that precludes the safe deployment/removal of the neurothrombectomy device
6. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)