Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke
Condition: Stroke, Acute
MeSH terms: Stroke
Intervention: Nerinetide (NA-1), 2.6 mg/kg; Placebo
Intervention description: Single intravenous infusion of nerinetide over 10 ± 1 minutes; Placebo Comparator: Placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1105.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute Ischemic Stroke; Endovascular Thrombectomy; Neuroprotection; Tat-NR2B9c; NA-1; Nerinetide

Summary:

      The ESCAPE-NA-1 study is designed to determine the safety and efficacy of the
      neuroprotectant, Nerinetide (NA-1), in reducing global disability in subjects with major
      acute ischemic stroke (AIS) with a small established infarct core and with good collateral
      circulation who are selected for endovascular revascularization.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Acute ischemic stroke (AIS) for immediate endovascular treatment

          2. Age 18 or greater.

          3. Onset (last-seen-well) time to randomization time within 12 hours.

          4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score
             (NIHSS) > 5 at the time of randomization.

          5. Pre-stroke (24 hours prior to stroke onset) independent functional status in
             activities of daily living with modified Barthel Index (BI) > 90 (95 or 100). Patient
             must be living in their own home, apartment or seniors lodge where no nursing care is
             required.

          6. Confirmed symptomatic intracranial occlusion, based on multiphase or dynamic
             computerized tomographic angiography (CTA), at one or more of the following locations:
             Intracranial carotid T/L, M1 middle cerebral artery (MCA). Functionally, when defining
             the M1 or the M2, the bulk of the MCA territory must be ischemic.

          7. Non-contrast computed tomography (NCCT) and CTA (multiphase or dynamic) for trial
             eligibility performed or repeated at ESCAPE-NA1 stroke centre with endovascular suite
             on-site.

          8. Endovascular treatment with declared first endovascular approach as either stent
             retriever or aspiration device, and intended to be initiated (arterial access) within
             60 minutes of baseline/qualifying NCCT and to first recanalization of 90 minutes.
             Study drug intended to be administered within 60 minutes of the baseline/qualifying
             NCCT.

          9. Signed informed consent from subject or legally authorized representative or, if
             required to enable inclusion by applicable national laws and regulations and the
             applicable independent review boards/Ethics Committee requirements for obtaining
             consent, from the investigator after consultation with an independent physician who is
             not otherwise participating in the trial.

        Exclusion Criteria:

          1. Evidence of a large core of established infarction defined as ASPECTS 0-4.

          2. Evidence of absence of collateral circulation on CTA (Collateral score of 0 or 1).

          3. Intent to use any endovascular device other than a stent retriever or clot aspiration
             device or intra-arterial medications as the initial thrombectomy approach.

          4. Intent to use any intravenous thrombolytic other than alteplase if intravenous
             thrombolysis is planned.

          5. No femoral pulses, very difficult endovascular access or extreme tortuosity of great
             vessels that is predicted to result in an inability to deliver timely endovascular
             therapy. Direct common carotid or radial/brachial/axillary access is permissible.

          6. Estimated or known weight > 120 kg or < 45 kg.

          7. Pregnancy; if a woman is of childbearing potential a urine or serum beta human
             chorionic gonadotropin (β-hCG) test is positive, or breastfeeding.

          8. Severe contrast allergy or absolute contraindication to iodinated contrast preventing
             endovascular intervention, including any contraindications listed in the prescribing
             information approved by local authorities (e.g., patients with decompensated heart
             failure as a contraindication for the use of VISIPAQUE™ 270 in Germany).

          9. Clinical history, past imaging or clinical judgment suggests that the intracranial
             occlusion is chronic or there is suspected intracranial dissection such that there is
             a predicted lack of success with endovascular intervention.

         10. Prior enrolment in the ESCAPE-NA1 trial or prior receipt of NA-1 for any reason.

         11. Severe known renal impairment defined as requiring dialysis (hemo- or peritoneal) or
             if known a creatinine clearance < 29 mL/min.

         12. Patient has a severe or fatal comorbid illness that will prevent improvement or
             follow-up.

         13. Patient cannot complete follow-up treatment due to co-morbid non-fatal illness or they
             are known to be a visitor to the city or any other known reason for which follow-up
             would be impossible (e.g. incarcerated in a federal prison).

         14. Participation in another clinical trial investigating a drug, medical device, or a
             medical procedure in the 30 days preceding study inclusion.