Inpatient Trials

Arcadia
Aspire
Axiomatic -BMS
Charm
Most
Saturn
SleepSmart
Timeless
BAF-312
Comets
Domino
Slam

TIA or Minor Ischemic Stroke

Acute Ischemic Stroke

ARCADIA

  • INCLUSION CRITERIA:
    1. Age ≥45 years.
    2. Clinical diagnosis of ischemic stroke + brain imaging to rule out hemorrhagic stroke.
    3. Modified Rankin Scale (MRS) score ≤4.
    4. Ability to be randomized no later than 120 days after stroke onset.
    5. ESUS, defined as all of the following:
      • Stroke that is not lacunar.
      • Absence of extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis of the artery supplying the area of ischemia. Patients must undergo vascular imaging of the extracranial and intracranial vessels using either catheter angiography, CT angiogram (CTA), MR angiogram (MRA), or ultrasound, as considered appropriate by the treating physician and local principal investigator.
      • No major-risk cardioembolic source of embolism, including AF, intracardiac thrombus, mechanical prosthetic cardiac valve, atrial myxoma or other cardiac tumors, mitral stenosis, myocardial infarction within the last 4 weeks, left ventricular ejection fraction <30%, valvular vegetations, or infective endocarditis). Patent foramen ovale is not an exclusion.
      • No other specific cause of stroke identified, such as arteritis, dissection, migraine, vasospasm, drug abuse, or hypercoagulability.
  • EXCLUSION CRITERIA:
    1. History of AF, AF on 12-lead ECG, or any AF of any duration during heart-rhythm monitoring prior to randomization.
    2. Clear indication for treatment-dose anticoagulant therapy, such as venous thromboembolism or a mechanical heart valve.
    3. Left ventricular ejection fraction <30%.
    4. Definite indication for antiplatelet agent (e.g., aspirin or clopidogrel after implantation of a coronary artery stent).
    5. History of spontaneous intracranial hemorrhage.
    6. Chronic kidney disease with serum creatinine ≥2.5 mg/dL.
    7. Active hepatitis or hepatic insufficiency with Child-Pugh score B or C (see MOP for definition).
    8. Clinically significant bleeding diathesis.
    9. Anemia (hemoglobin <9 g/dL) or thrombocytopenia (<100 x 109/L) that is chronic in the judgment of the investigator.
    10. GI bleeding within the past year considered clinically significant by the investigator.
    11. Pregnancy risk: − Female patient who is known to be pregnant.
      • Female patient who is sexually active and premenopausal without a negative pregnancy test performed after stroke onset.
      • Female patient who is sexually active and premenopausal, and who does not commit to adequate birth control.
      • Male patient who is sexually active with a premenopausal female partner, and who does not commit to adequate birth control.
    12. Known allergy or intolerance to aspirin or apixaban.
    13. Concomitant participation in another clinical trial involving a drug or acute stroke intervention.
    14. Considered by the investigator to have a condition that precludes follow-up or safe participation in the trial.
    15. Inability to obtain written, informed consent from patient or surrogate for trial participation.

ASPIRE

  • INCLUSION CRITERIA:
    1. Age at least 18 years
    2. Intracerebral hemorrhage (ICH) (including primary intraventricular hemorrhage) confirmed by brain CT or MRI
    3. Can be randomized within 14-120 days after ICH onset
    4. Non-valvular AF (defined as atrial fibrillation or atrial flutter), documented by electrocardiography or a physician-confirmed history of AF
    5. CHA2DS2-VASc score21 ≥ 2
    6. Provision of signed and dated informed consent form by patient or legally authorized representative
    7. Expected to comply with all study procedures and be available for duration of the study
    8. For females of reproductive potential: use of highly effective contraception
  • EXCLUSION CRITERIA:
    1. History of ICH before index event
    2. Active infective endocarditis
    3. Lobar ICH with high-risk cerebral amyloid angiopathy
    4. Clear indication for anticoagulant drugs (e.g., requires anticoagulation for DVT or PE) or antiplatelet drugs (e.g., requires aspirin or clopidogrel for recent MI)
    5. Previous or planned left atrial appendage closure
    6. Clinically significant bleeding diathesis
    7. Serum creatinine ≥2.5 mg/dL
    8. Active hepatitis or hepatic insufficiency with Child-Pugh score B or C
    9. Anemia (hemoglobin <8 g/dL) or thrombocytopenia (<100 x 109/L) that is chronic in the judgment of the investigator
    10. Life expectancy <1 year
    11. Pregnant or breastfeeding
    12. Known allergy to aspirin or apixaban
    13. Concomitant participation in a competing therapeutic trial
    14. Considered by the investigator to have a condition that precludes safe participation in the trial
    15. Unwilling to discontinue open-label anticoagulant or antiplatelet medications

BMS – AXIOMATIC

  • INCLUSION CRITERIA:
    1. Ability to provide informed consent by patient or legally authorized representative.
    2. Identified within 48 hours of onset of signs and/or symptoms of stroke or TIA.
    3. Aged ≥40 years at time of informed consent.
    4. mRS ≤3 BEFORE index event
    5. Ischemic stroke:
      1. Non-lacunar, acute brain infarction detected by CT/MRI and relevant to the clinical symptoms AND
      2. NIHSS ≤5 at time of randomization AND
      3. Evidence of relevant intracranial or cervical arterial atherosclerotic plaque, ulceration or thrombus in a feeding artery documented by imaging (Atherosclerotic plaque does not need to be severe/stenotic, but must be visible. Participants with complete occlusion of a cervical carotid or ICA should be excluded.)
    6. OR TIA:
      1. Acute onset neurological deficit attributable to focal ischemia of the brain by history or examination, with complete resolution of the deficit and no brain infarction on imaging AND
      2. ABCD2 score ≥ 6 or motor symptoms AND
      3. Evidence of relevant intracranial or cervical arterial atherosclerotic plaque, ulceration or thrombus in a feeding artery documented by imaging. (Atherosclerotic plaque does not need to be severe/stenotic, but must be visible. Participants with complete occlusion of a cervical carotid or ICA should be excluded.)
    7. Able to be evaluated by study-specific MRI within 48 hours of index event and prior to randomization
    8. No contraindication to clopidogrel or aspirin and suitable for treatment with aspirin 100 mg per day for at least 90 days
    9. Woman of childbearing potential with negative serum or urine pregnancy test within 24hrs prior to start of study drug. Must agree to follow instructions for contraceptive methods for duration of study treatment plus 5 halflives of study treatment plus 30 days (duration of ovulatory cycle) for a total of 34 days post-treatment completion.
    10. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment plus 5 half-lives of the study treatment, plus 90 days (duration of sperm turnover) for a total of 94days post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time
  • EXCLUSION CRITERIA:
    1. Predicted inability to swallow study medication
    2. Women who are pregnant or breastfeeding
    3. Any condition that, in opinion of Investigator, contraindicates anticoagulant therapy or would have unacceptable risk of bleeding such as large infarct volume (per Investigator discretion) or uncontrolled hypertension
    4. Hemorrhage, tumor, arteritis, large vessel dissection, arteriovenous malformation, or other pathology that could account for index symptoms (must be excluded by CT or MRI interpreted locally)
    5. Symptomatic carotid stenosis for which endarterectomy or stenting is planned within 90 days
    6. Use of thrombolytic therapy or mechanical thrombectomy for treatment of index event
    7. Any condition for which chronic anticoagulation is recommended (NVAF, DVT, PE etc.)
    8. Requirement for continued use of dual antiplatelet therapy for more than 21 days or non-aspirin antiplatelet therapy or anticoagulant for another medical condition (e.g. prophylaxis for venous thromboembolism)
    9. History of hemorrhage into the brain, subarachnoid hemorrhage, subdural hematoma, or spinal cord hemorrhage except cerebral microbleeds (defined as rounded foci of <10 mm in size that appear hypointense and distinct from vascular flow voids, leptomeningeal hemasiderosis, or non-hemorrhagic subcortical mineralization on T2* weighted MRI) and minor hemorrhagic transformation of prior infarct manifesting as scattered petechiae
    10. History of clinically meaningful hepatic disease and/or clinically significant abnormal liver function
    11. Intracranial tumor (except meningioma, which is permitted) or aneurysm >5 mm or AVM
    12. History of end-stage renal disease with eGFR <15 mL/min/1.73m2, or requiring dialysis
    13. Any investigational drug or placebo exposure within 4 weeks of study drug administration
    14. Any prior exposure to BMS-986177
    15. Planned use of anticoagulants including warfarin or other vitamin K antagonists, oral thrombin and Factor Xa inhibitors, bivalirudin, hirudin, argatroban, unfractionated and low molecular weight heparins, with the exception of heparin or LMWH used to maintain patency of indwelling catheters (note: patients who received 1 or 2 doses of UFH or LMWH for DVT prophylaxis prior to randomization can be enrolled)
    16. Planned concomitant use of omeprazole or esomeprazole after randomization for the duration of clopidogrel treatment (e.g., H2 blockers, except cimetidine, and other PPIs are allowed)
    17. Anticipated concomitant chronic (>14 days) use of systemic nonsteroidal anti-inflammatory drugs. NSAIDs, including COX-2 inhibitors, use prior to randomization is allowed
    18. Use of strong CYP3A4/P-gp inhibitors/inducers within 7 days of randomization or the need for ongoing treatment with concomitant oral/IV therapy during the study.
    19. Inability to comply with the following concomitant medication restrictions (listed in section 7.7.1 of the protocol):
      1. St John’s Wort within 7 days prior to randomization and throughout the study
      2. strong CYP3A4 inhibitors
      3. strong CYP3A4 inducers
    20. Any of the following laboratory results outside of ranges specified below prior to study treatment administration, confirmed by repeat:
      1. Hemoglobin < 9 g/dL
      2. Platelet count < 100,000 mm3
      3. aPTT > 1.4x ULN
      4. INR ≥ 1.7
      5. AST or ALT >3x ULN
    21. Any of the following on 12-lead ECG prior to randomization:
      1. Atrial fibrillation or atrial flutter
      2. Complete heart block or Mobitz 2 second-degree heart block
    22. Known positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 and HIV-2 antibody. Note: participants with a treated and completely resolved hepatitis C infection without any sequelae are permitted
    23. History of allergy to BMS-986177, clopidogrel, aspirin, or aspirin-containing compounds, or history of any significant drug allergy (such as anaphylaxis), or history of drug-induced hematologic or hepatic abnormalities
    24. Prisoners or participant who is involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric of physical (eg, infectious disease) illness
    25. Participant in whom MRI procedures cannot be performed
      1. History of claustrophobia
      2. Weight greater than that allowable by MRI table
      3. MRI-incompatible cardiac device, aneurysm clip, cochlear implants, spinal nerve stimulator, infusion pump, etc.
      4. Tattoos or permanent makeup near eye
      5. Metallic fragments in eyes/orbits or in vicinity of brain or major neurovascular structures, or shrapnel at any place in the body
      6. Employment history involving exposure to welding, unless absence of metallic fragments is documented by X-ray

CHARM

  • INCLUSION CRITERIA:
    1. Ability to provide informed consent by patient or legally authorized representative.
    2. A clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA territory involvement in addition to primary MCA territory stroke is acceptable).
    3. AGES: ONLY Ages 18-70yrs, inclusive, at time of ICF
    4. Screening NIHSS ≥10.
    5. Prior to the current stroke, no significant disability in the opinion of the Investigator (able to independently perform all duties and activities of daily living without assistance from a caregiver, spouse, or another person).
    6. A large hemispheric infarction defined, in order of preference, as either:
      • a magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) lesion volume of 80 to 300 cm3, or
      • a computed tomography perfusion (CTP) core lesion volume of 80 to 300 cm3, or
      • an Alberta Stroke Program Early computed tomography (CT) Score (ASPECTS) on non-contrast computed tomography (NCCT) of 1 to 5 with involvement of at least 2 defined cortical regions, if lesion volume from MRI DWI or CTP is not available.
    7. Study drug treatment infusion should be initiated as soon as possible but no later than 10 hours after time of symptom onset, if known, or the time last known normal (if time to symptom onset is unknown).
  • EXCLUSION CRITERIA:
    1. In the judgment of the Investigator, the subject is likely to have supportive care withdrawn in the first day.
    2. Commitment to decompressive craniectomy (DC) prior to enrollment.
    3. Evidence (clinical or imaging) of concurrent infarction in the contralateral hemisphere deemed by the Investigator to be sufficiently serious so as to affect functional outcome. This would include, for example, a contralateral ACA infarct that leads to bilateral leg paralysis.
    4. Clinical signs of herniation, e.g., 1 or 2 dilated, fixed pupils; unconsciousness related to edema (i.e., ≥2 on item 1a on the NIHSS); and/or loss of other brain stem reflexes, attributable to edema or herniation according to the Investigator’s judgment.
    5. Brain hemorrhage (other than small petechial/punctate hemorrhages) on NCCT/MRI.
    6. NCCT/MRI evidence of anteroseptal/pineal shift >2 mm prior to enrollment.
    7. Use of intra-arterial thrombolytic agents, alone or in combination with thrombectomy.
    8. Patients who are currently being considered for thrombectomy and/or IV thrombolysis may not be randomized into the study until these procedures have been completed OR the decision not to perform them has been made. These treatments should not be delayed for study screening procedures. When thrombectomy is performed prior to randomization, study eligibility must be assessed using inclusion criterion #7.
    9. Subjects with, in the opinion of the Investigator, life expectancy < 3 months not related to current LHI, or those unlikely to be compliant with follow up.
    10. Subjects in whom a peripheral IV line cannot be placed.
    11. Subjects with mental disability (prior to qualifying LHI) or wards of the state.
    12. Subjects whose stroke symptoms are rapidly improving and are not expected in the opinion of the Investigator to have NIHSS≥10 at the time of randomization.
    13. Medical History:
      1. Known allergy to BIIB093 or to another sulfonylurea drug or any of the components of the formulated BIIB093 or matching placebo.
      2. Subjects who are known to have taken oral glibenclamide within the past 10 hours.
      3. Known history of clinically significant severe form of renal or hepatic disorder, in the Investigator’s opinion (e.g., dialysis or cirrhosis, respectively).
      4. Known history of chronic obstructive pulmonary disease that, in the judgment of the Investigator, is severe (e.g., requiring home oxygen).
      5. Known history of clinically significant hypoglycemia, in the Investigator’s opinion based on known medical history or local screening laboratory assessments (i.e. screening blood glucose <70 mg/dL [~3.9 mmol/L]).
      6. Subjects who have or have ever had diabetic ketoacidosis or diabetic coma/precoma.
      7. Acute ST elevation myocardial infarction (MI), and/or acute decompensated heart failure, and/or QTc >520 msec, and/or admission for an acute coronary syndrome, MI, cardiac arrest, or non-voluntary coronary intervention (percutaneous coronary intervention or coronary artery surgery) within the past 3 months.
      8. New York Heart Association heart failure III/IV (class III: marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m); class IV: severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients).
      9. Known cardiac ventricular tachycardia.
      10. Subjects with known glucose-6-phosphate dehydrogenase enzyme deficiency.
      11. Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) that required hospitalization or was clinically significant in the opinion of the Investigator within 3 days prior to Screening.
    14. Other:
      1. Females who are pregnant or women of childbearing potential with a positive pregnancy test at time of admission.
      2. Nursing women who are unable to stop breastfeeding during study treatment infusion and for 7 days following the end of study treatment infusion.
      3. Known current participation or known history of participation in any other investigational study that involved treatment with an investigational drug within 14 days prior to enrollment.
      4. Inability to comply with study requirements.
      5. Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the subject unsuitable for enrollment.

MOST

  • INCLUSION CRITERIA:
    1. Acute ischemic stroke patients
    2. Treated with 0.9mg/kg IV rt-PA within 3 hours of stroke onset or time last known well
    3. Age ≥ 18
    4. NIHSS score ≥ 6 prior to IV rt-PA
    5. Able to receive assigned study drug within 60 minutes but no later than 75 minutes of initiation of IV rt-PA
  • EXCLUSION CRITERIA:
    1. Known allergy or hypersensitivity to argatroban or eptifibatide
    2. Previous stroke in the past 90 days
    3. Previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation
    4. Clinical presentation suggested a subarachnoid hemorrhage, even if initial CT scan was normal
    5. Surgery or biopsy of parenchymal organ in the past 30 days
    6. Trauma with internal injuries or ulcerative wounds in the past 30 days
    7. Severe head trauma in the past 90 days
    8. Systolic blood pressure persistently >180mmHg post-IV rt-PA despite antihypertensive intervention
    9. Diastolic blood pressure persistently >105mmHg post-IV rt-PA despite antihypertensive intervention
    10. Serious systemic hemorrhage in the past 30 days
    11. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR >1.5
    12. Positive urine pregnancy test for women of child bearing potential
    13. Glucose <50 or >400 mg/dl
    14. Platelets <100,000/mm3
    15. Hematocrit <25 %
    16. Elevated PTT above laboratory upper limit of normal
    17. Creatinine > 4 mg/dl
    18. Ongoing renal dialysis, regardless of creatinine
    19. Received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin) in full dose within the previous 24 hours
    20. Abnormal PTT within 48 hours prior to randomization after receiving heparin or a direct thrombin inhibitor (such as bivalirudin, argatroban, dabigatran or lepirudin)
    21. Received Factor Xa inhibitors (such as Fondaparinaux, apixaban or rivaroxaban) within the past 48 hours
    22. Received glycoprotein IIb/IIIa inhibitors within the past 14 days
    23. Pre-existing neurological or psychiatric disease which confounded the neurological or functional evaluations e.g., baseline modified Rankin score >3
    24. Other serious, advanced, or terminal illness or any other condition that the investigator felt would pose a significant hazard to the patient if rt-PA, eptifibatide or argatroban therapy was initiated
      1. Example: known cirrhosis or clinically significant hepatic disease
    25. Current participation in another research drug treatment or interventional device trial – Subjects could not start another experimental agent until after 90 days
    26. Informed consent from the patient or the legally authorized representative was not or could not be obtained
    27. High density lesion consistent with hemorrhage of any degree
    28. Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT Scan. Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment

SATURN

  • INCLUSION CRITERIA:
    1. Age ≥ 50 years.
    2. Spontaneous lobar ICH within 7 days prior to randomization confirmed by CT or MRI scan. Lobar ICH will be defined as ICH involving cortical or subcortical locations and situated ≥1cm from the body of the ipsilateral lateral ventricle and not originating from any of the following deep structures (thalamus, putamen, globus pallidus, caudate, or internal capsule).
    3. Patient was taking a statin drug at the onset of the qualifying/index ICH
    4. Randomization must be carried out within 7 days of the onset of the qualifying ICH
    5. Patient or legally authorized representative, after consultation with physicians, agrees to be randomized to statin continuation (restart) vs. discontinuation.
  • EXCLUSION CRITERIA:
    1. Suspected secondary cause for the qualifying ICH, such as an underlying vascular abnormality or tumor, trauma, venous infarction, or hemorrhagic transformation of an ischemic infarct.
    2. History of recent myocardial infarction (attributed to coronary artery disease) or unstable angina within the previous 3 months
    3. Diabetic patients with history of myocardial infarction or coronary revascularization
    4. History of familial hypercholesterolemia
    5. Patients receiving proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors
    6. Known diagnosis of severe dementia
    7. Inability to obtain informed consent
    8. Patient known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, or other obvious reasons for noncompliance, such as unable to adhere to the protocol specified visits/assessments.
    9. Life expectancy of less than 24 months due to co-morbid terminal conditions.
    10. Pre-morbid mRS >3
    11. ICH score >3 upon presentation.
    12. Contraindications to continuation/resumption of statin therapy, such as significant elevations of serum creatinine kinase and/or liver transaminases, and rhabdomyolysis
    13. Women of childbearing potential, defined as pre-menopausal women capable of becoming pregnant (Post-menopausal women, women who are surgically sterilized, and women who are known to be infertile can be enrolled in the trial).
    14. Concurrent participation in another research protocol for investigation of experimental therapy.
    15. Indication that withdrawal of care will be implemented for the qualifying ICH.

SLEEPSMART

  • INCLUSION CRITERIA:
    1. Age ≥18
    2. TIA with ABCD2 ≥4 or ischemic stroke (as defined in the outcome section84), within the prior 14 days.
  • EXCLUSION CRITERIA:
    1. Pre-event inability to perform all of own basic ADLs
    2. Unable to obtain informed consent from subject or legally authorized representative
    3. Incarcerated
    4. Known pregnancy
    5. Current mechanical ventilation (can enroll later if this resolves) or tracheostomy
    6. Current use of positive airway pressure, or use within one month prior to stroke
    7. Anatomical or dermatologic anomaly that makes use of CPAP interface unfeasible
    8. Severe bullous lung disease
    9. History of prior spontaneous pneumothorax or current pneumothorax
    10. Hypotension requiring current treatment with pressors (can enroll later if this resolves)
    11. Other specific medical circumstances that conceivably, in the opinion of the site PI, coul render the patient at risk of harm from use of CPAP
    12. Massive epistaxis or previous history of massive epistaxis
    13. Cranial surgery or head trauma within the past 6 months, with known or possible CSF leak or pneumocephalus
    14. Recent hemicraniectomy or suboccipital craniectomy (i.e. those whose bone has not yet been replaced), or any other recent bone removal procedure for relief of intracranial pressure
    15. Current receipt of oxygen supplementation >4 liters per minute
    16. Current contact, droplet, respiratory/airborne precautions

TIMELESS

  • HOTLINE #: 1(888)316-3335
  • INCLUSION CRITERIA:
    1. Patient/legally authorized representative has signed the Informed Consent Form
    2. Age > 18 years
    3. AIS symptom onset within 4.5 to 24 hours
    4. 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 present within the 4.5- to 24-hour time limits).
    5. All study-related treatment needs to be initiated within 24 hours.
    6. Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the ICA, M1, or M2 vessels
    7. Functionally independent (mRS 0-2) prior to stroke onset
    8. Baseline NIHSS >5 and that remains >5 immediately prior to randomization
    9. Neuroimaging: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial, w/wo tandem MCA lesions) by MRA or CTA AND target mismatch profile on CT perfusion or MRI (ischemic core volume <70 mL, mismatch ratio is >1.8 and mismatch volume is >15 mL)
    10. The mismatch volume is determined by FDA-approved imaging software in real time based on the difference between the ischemic core lesion volume and the Tmax>6s lesion volume. If both a CT perfusion and a multimodal MRI scan are performed prior to enrollment, the later of the 2 scans is assessed to determine eligibility. For patients screened with MRA, only an intracranial MRA is required (cervical MRA is not required). Cervical and intracranial CTA are typically obtained simultaneously in patients screened with CTA, but only the intracranial CTA is required for enrollment.
    11. Alternative neuroimaging:
    12. If CTA (or MRA) is technically inadequate: Tmax>6s perfusion deficit consistent with an ICA or M1, M2 occlusion AND target mismatch profile (ischemic core volume <70 mL, mismatch ratio >1.8 and mismatch volume >15 mL as determined by RAPID software)
    13. If MRP is technically inadequate: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial; w/wo 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 for an M1 or ICA occlusion and <15 mL for an M2 occlusionIf CTP is technically inadequate:  patient can be screened with MRI and randomized if neuroimaging criteria are met.
    14. Ability to comply with the study protocol, in the investigator’s judgment
  • EXCLUSION CRITERIA:
    1. General:
      1. Current participation in another investigational drug or device study.
      2. Known hypersensitivity or allergy to any ingredients of tenecteplase
      3. Active internal bleeding
      4. Known bleeding diathesis
      5. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR >1.7
      6. Use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban)
      7. Treatment with a thrombolytic within the last 3 months prior to randomization
      8. Intracranial neoplasm (except small meningioma), arteriovenous malformation, or aneurysm
      9. Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
      10. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluation
      11. Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg)
      12. Baseline platelet count <100,000/|aL (results must be available prior to treatment)
      13. Baseline blood glucose >400 mg/dL (22.20 mmol/L)
      14. Baseline blood glucose <50 mg/dL needs to be normalized prior to randomization
      15. Clot retrieval attempted using a neurothrombectomy device prior to randomization
      16. Intracranial or intraspinal surgery or trauma within 2 months
      17. Other serious, advanced, or terminal illness (investigator judgment) or life expectancy is less than 6 months
      18. History of acute ischemic stroke in the last 90 days
      19. History of hemorrhagic stroke
      20. Presumed septic embolus; suspicion of bacterial endocarditis
      21. Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the patient if an endovascular procedure was to be performed
      22. Pregnant
    2. Imaging:
      1. Unable to undergo a contrast brain perfusion scan with either MRI or CT
      2. Extensive early ischemic change (hypodensity) on non-contrast CT estimated to be >1/3 MCA territory, or significant hypodensity outside the Tmax>6s perfusion lesion that invalidates mismatch criteria (if patient is enrolled based on CT perfusion criteria)
      3. Significant mass effect
      4. Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion)
      5. Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation

Acute Intracerebral Hemorrhage

BAF

  • INCLUSION CRITERIA:
    1. Aged 18 to 85 years (inclusive)
    2. Spontaneous, supratentorial intracerebral hemorrhage in cerebral cortex or deep brain structures (putamen, thalamus, caudate, and associated deep white matter tracts) with a volume ≥ 10 mL but ≤ 60 mL (calculated by the ABC/2 method) determined by routine clinical MRI or CT.
    3. < 24 hrs from last known normal
    4. Glasgow Coma Scale (GCS) best motor score no less than 5(brings hands above clavicle on stimulus to head or neck).
  • EXCLUSION CRITERIA:
    1. Use of other investigational drugs within 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline (for biologics), whichever is longer.
    2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (e.g., fingolimod).
    3. Current use of concomitant medications with potent CYP2C9/3A4 inhibitory or induction potential.
    4. Infratentorial (midbrain, pons, medulla, or cerebellum) ICH.
    5. Candidates for surgical hematoma evacuation or other urgent surgical intervention (i.e., surgical relief of increased intracranial pressure) on initial presentation. If during the treatment period surgical hematoma evacuation or surgical intervention to lower intracranial pressure becomes indicated, the investigational treatment should be stopped.
    6. Patients with intraventricular hematoma extension, with or without hydrocephalus, on initial presentation.
    7. Secondary ICH due to:
      • aneurysm
      • brain tumor
      • arteriovenous malformation
      • thrombocytopenia, defined as platelet count of <150,000/µl
      • known history of coagulopathy
      • acute sepsis
      • traumatic brain injury (TBI)
      • disseminated intravascular coagulation (DIC)
    8. Prior disability due to other disease compromising mRS evaluation defined as an estimated mRS score (by history) of ≥ 3 before ICH. 
    9. Preexisting unstable epilepsy.
    10. Patients with active systemic bacterial, viral or fungal infections.
    11. Concomitant drug-related exclusion criteria:
      • Intravenous immunoglobulin, immunosuppressive and/or chemotherapeutic medications.
      • Moderate immunosuppressives (e.g. azathioprine, methotrexate) and/or fingolimod within 2 months prior to randomization.
      • Stronger immunosuppressives (e.g. cyclophosphamide, immunosuppressive mAb) within (minimally) 6 months prior to randomization, or longer with long-lasting immunosuppressive medications as determined by the investigator.
    12. Cardiovascular exclusion criteria:
      • Cardiac conduction or rhythm disorders including sinus arrest or sino-atrial block, heart rate <50 bpm, sick-sinus syndrome, Mobitz Type II second degree AV block or higher grade AV block, or preexisting atrial fibrillation (either by history or observed at screening).
      • PR interval >220 msec. Long QT syndrome or QTcF prolongation >450 msec in males or >470 msec in females on screening electrocardiogram (ECG).
      • Patients receiving treatment with QT-prolonging drugs having a long half-life (e.g., amiodarone).
    13. Any of the following abnormal laboratory values prior to randomization:
      • White blood cell (WBC) count < 2,000/μl (< 2.0 x 109/L)
      • Lymphocyte count < 800/μl (< 0.8 x 109/L)
    14. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
    15. Patients with any other medically unstable condition or serious laboratory abnormality as determined by the investigator.

Investigator Initiated Trials

COMETS

  • INCLUSION CRITERIA:
    1. Age ≥ 18 years
    2. Acute ischemic stroke with radiographic evidence of occlusion of the internal carotid artery and/or middle cerebral artery on either side of the brain
    3. Patient will undergoing mechanical thrombectomy for acute stroke
    4. Willingness and ability to sign informed consent by patient or legally acceptable surrogate decision-maker
  • EXCLUSION CRITERIA:
    1. Bilateral arterial occlusion
    2. Hemicraniectomy or other skull defect that would interfere with monitoring.
    3. History of brain mass (other than meningioma)
    4. Pregnancy
      1. Women of child-bearing age must have a negative pregnancy test (urine or serum) prior to enrollment (which is performed as part of standard care)
    5. Any other illness or condition that the investigator feels would pose a hazard to the subject from participation in the study

DOMINO

  • INCLUSION CRITERIA:
    1. Age > 18
    2. Acute ischemic stroke in the territory of the anterior, middle, or posterior cerebral artery, on either side of the brain
    3. Study can be initiated within 72 hours of stroke symptom onset
    4. Ability and willingness to sign informed consent
  • EXCLUSION CRITERIA:
    1. History of any neurological disease
    2. History of stroke or transient ischemic attack
    3. Known cerebrovascular abnormality
    4. History of congestive heart failure
    5. History of chronic pulmonary disease such as asthma or COPD
    6. Presence of pneumonia or active pulmonary infection
    7. Current use of any NO donor medication (sodium nitroprusside or nitroglycerin)
    8. Age < 18 years
    9. Skull defect that would interfere with CBF monitoring
    10. Pregnancy (urine or blood tests will not be performed)
    11. Structural brain lesion
    12. Prior neurosurgical procedure
    13. History of psychiatric disease
    14. Any medical condition that the clinical investigator feels would pose a hazard to the subject if he/she participated in the study
    15. Cognitive impairment

SLAM

  • INCLUSION CRITERIA:
    1. Age > 18
    2. For cases, admission to the Stroke Inpatient Service with a diagnosis of acute ischemic stroke. NIHSS≥1, including at least 1 point for limb weakness.  At least half of the stroke patients must have at least 2 points on the NIHSS for limb weakness.
    3. For controls, admission to the hospital with a TIA, normal MRI, and normal neurologic exam, admission to the Epilepsy Monitoring Unit for differential diagnosis of transient neurologic spells with a normal MRI and normal neurologic exam, or recent cardiac surgery.
  • EXCLUSION CRITERIA:
    1. Any medical or psychological conditions that, in the opinion of the investigator, would compromise the subject’s safety or successful participation in the study.
    2. A limb amputation above the wrist in the upper extremities and the ankle in the lower extremities.
    3. For controls:
      1. History of prior stroke
      2. Evidence of prior brain injury on MRI when this data is available, excluding mild small vessel ischemic disease
      3. Evidence of any focal neurologic findings on exam including asymmetric limb weakness or neglect