POSITIVE Stroke Clinical Trial

Intravenous (IV) tissue plasminogen activator (tPA) administration has been shown to be safe
and effective for treatment of AIS within 3 hours of symptom onset, and newer evidence has
shown potential benefit out to 4.5 hours. Mechanical thrombectomy for AIS patients has been
shown in clinical trials to be safe up to 8 hours after symptom onset. The rapid progression
of thrombectomy devices over the last several years has resulted in faster recanalization
times while maintaining a high degree of safety. This has resulted in improved patient
outcomes, similar to prior randomized trial data showing improved outcomes over medical
therapy or earlier devices. Data from the MERCI trial suggests that patients > 85 as well as
those with a baseline NIHSS score > 30 are unlikely to benefit from thrombectomy. Patients
with rapidly improving neurologic deficits likely will have an excellent recovery with
conventional care, precluding the ability to detect a beneficial treatment effect of
thrombectomy.

Pilot data incorporating physiologic imaging has shown that appropriate patients can be
selected for thrombectomy. This selection methodology has shown the ability to maintain the
same level of safety and efficacy as those patients treated in the highly selective
environment of a clinical trial, despite presenting far beyond accepted time based standards.
Vertebrobasilar occlusion patients are excluded to maintain a homogenous study population,
particularly since no data currently is available addressing the comparability of imaging
penumbral patterns in the anterior vs. posterior circulation. This has also been shown to be
reproducible at multiple centers and with different imaging modalities. However, all
prospective interventional stroke studies performed to date have been restricted by the
8-hour time window.

Inclusion Criteria:

1. Age 18 and older (i.e., candidates must have had their 18th birthday)

2. NIHSS ≥8 at the time of neuroimaging

3. Presenting or persistent symptoms within 6-12 hours of when groin puncture can be
obtained

4. Neuroimaging demonstrates large vessel proximal occlusion (distal ICA through MCA M1
bifurcation)

5. The operator feels that the stroke can be appropriately treated with traditional
endovascular techniques (endovascular mechanical thrombectomy without adjunctive
devices such as stents)

6. Pts are within 6-12 hours of symptom onset, that have received IV-tPA without
improvement in symptoms are eligible for this study. Patients presenting earlier than
6 hours should be treated according to local standard of care.

7. Pre-event Modified Rankin Scale score 0-1

8. Consenting requirements met according to local IRB

Exclusion Criteria:

1. Patient is less than 6-hours from symptom onset

2. Rapidly improving neurologic examination

3. Absence of large vessel occlusion on non-invasive imaging

4. Known or suspected pre-existing (chronic) large vessel occlusion in the symptomatic
territory

5. Absence of an associated large penumbra as defined by physiologic imaging according to
standard of practice at the participating institution

6. Any intracranial hemorrhage in the last 90 days

7. Known irreversible bleeding disorder

8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or
oral anticoagulant therapy with INR > 2.5 or institutionally equivalent prothrombin
time of 2.5 times normal

9. Platelet count < 100 x 103 cells/mm3 or known platelet dysfunction

10. Inability to tolerate, clinically documented evidence in medical history of adverse
reaction to, or contraindication to medications used in treatment of the stroke

11. Contraindication to CT and MRI (i.e., iodine contrast allergy or other condition that
prohibits imaging from either CT or MRI)

12. Known allergy to contrast used in angiography that cannot be medically controlled

13. Relative contraindication to angiography (e.g., serum creatinine > 2.5 mg/dL)

14. Women who are currently pregnant or breast-feeding (Women of child-bearing potential
must have a negative pregnancy test prior to the study procedure (either serum or
urine)

15. Evidence of active infection (indicated by fever at or over 99.9 °F and/or open
draining wound) at the time of randomization

16. Current use of cocaine or other vasoactive substance

17. Any comorbid disease or condition expected to compromise survival or ability to
complete follow-up assessments through 90 days

18. Patients who lack the necessary mental capacity to participate or are unwilling or
unable to comply with the protocol's follow up appointment schedule (based on the
investigator's judgment)

Head CT or MRI Scan Exclusion Criteria

- Presence of blood on imaging (subarachnoid hemorrhage (SAH), intracerebral hemorrhage
(ICH), etc.)

- High density lesion consistent with hemorrhage of any degree

- Significant mass effect with midline shift

- Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on
the baseline CT scan or ASPECTS of < 7; Sulcal effacement and/or loss of grey-white
differentiation alone are not contraindications for treatment