Inpatient Trials

Arcadia
Aspire
Charm
Most
Presta
Saturn
Select-2
SleepSmart
Timeless
Discovery
Comets
Domino
Recast
Slam
CH in LVAD
Optical Biomarkers of CVD

All Inpatient Strokes –

DISCOVERY Ann

  • INCLUSION CRITERIA:
    1. Age > 18 years
    2. Admitted to the hospital with a diagnosis of AIS, ICH, or aSAH
    3. Radiographic confirmatory evidence of: (1) AIS (based on a focal area of restricted diffusion on MRI), (2) non-traumatic ICH (based on evidence of acute parenchymal hemorrhage CT or brain MRI) or (3) non-traumatic acute aSAH (based on evidence of subarachnoid hemorrhage on CT or MRI and evidence of aneurysm on CT angiography, MR angiography, or conventional catheter-based angiography)
    4. Able to complete baseline visit in person or by phone within 6 weeks of stroke onset
    5. Able to provide informed consent by self or proxy
    6. Fluent in English or Spanish prior to stroke onset
  • EXCLUSION CRITERIA:
    1. Documented history of pre-stroke dementia or fails dementia pre-screen
    2. Concurrently enrolled into a study that is not approved under the DISCOVERY Co-Enrollment Policy
    3. Unable to complete study protocol (advanced directives such as comfort measures only, or inability to complete the study due to severe medical/behavioral co-morbidities), as determined by physician investigator during screening process
    4. Contraindication to MRI: presence of electrically, magnetically, or mechanically activated implants (such as cardiac pacemakers, cochlear implants, implanted pumps); or metallic clips in the brain

Acute Ischemic Stroke

ARCADIA Devin

  • 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.

ASPIREMaryLiz

  • 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 14-180 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 score20 ≥ 2
    6. Provision of signed and dated informed consent form by patient or legally authorized representative
    7. For females of reproductive potential: use of highly effective contraception
  • EXCLUSION CRITERIA:
    1. Index event is hemorrhagic transformation of brain infarction or hemorrhage into a tumor
    2. History of an earlier ICH within 12 months preceding index event
    3. Active infective endocarditis
    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. Pregnant or breastfeeding
    11. Known allergy to aspirin or apixaban
    12. Concomitant participation in a competing therapeutic trial
    13. Considered by the investigator to have a condition that precludes safe or active participation in the trial
    14. Persistent, uncontrolled systolic blood pressure (≥180 mm Hg)
    15. ICH caused by an arteriovenous malformation (AVM) that has not yet been secured
  • Patient may be enrolled if exclusion resolves within 180 days of index ICH (e.g., blood pressure is controlled, AVM secured).

CHARM Devin

  • 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 Nichole

  • 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

PRESTANichole

  • INCLUSION CRITERIA:
    1. 18 to 85 years old, male and female
    2. mRS<=2 prior to stroke
    3. Ischemic or hemorrhagic stroke as diagnosed by vascular neurologist or as proven on magnetic resonance imaging (MRI) or non-contrast head computed tomography (NCHCT)
    4. 24 hours to 3 weeks after stroke onset or time last known well prior to detection of symptoms
    5. NIHSS>=3 and NIHSS<=15
    6. Creatinine Clearance of greater than or equal to 60 mL/min using the Cockroft-Gault equation.
    7. Have passed a swallow evaluation prior to drug administration
    8. The patient is an acute rehabilitation candidate or candidate for the Homeward Stroke Program
    9. Able to participate in administered tests
  • Note: Women and members of minority groups will be included in accordance with the NIH Policy on Inclusion of Women and Minorities as Participants in Research Involving Human Subjects.
  • EXCLUSION CRITERIA:
    1. Any degree of receptive aphasia
    2. Moderate or severe expressive aphasia
    3. Currently pregnant or plans to get pregnant
    4. Currently breastfeeding
    5. Any patient admitted with primary SAH on either non-contrast head CT or MRI brain
    6. Diagnosis of dementia or mild cognitive impairment prior to index stroke
    7. Prior limb amputation
    8. Currently prescribed or taking a primary anticholinergic medication
    9. Currently enrolled in any other investigational pharmacologic or procedural clinical trial
    10. Malignancy with active treatment
    11. History of prior stroke with residual impairment
    12. Current or prior neuroleptic use
    13. History of suicidality or psychosis (The Columbia Suicide Severity Ratings Scale (C-SSRS) will be administered at the screening visit to assess depression and suicidal thoughts for subject eligibility. Any subjects who indicate severe depression or suicidal thoughts and/or attempts within the last year will not be eligible)
    14. Prior history of seizures
    15. Prior treatment with amantadine
    16. Parkinson’s disease
    17. Amantadine allergy
    18. Elevated liver function tests (aspartate aminotransferase and alanine aminotransferase above the upper limit of normal)

SELECT-2Nichole

  • INCLUSION CRITERIA:
    1. Adults (18-85 years) with the final diagnosis of an acute ischemic stroke
    2. NIHSS ≥ 6
    3. Last known well to groin puncture or medical management between 0 to 24 hours
    4. Pre-stroke modified Rankin Scale score of 0-1
    5. Eligible for thrombectomy with stent retriever or medical management
    6. Signed Informed Consent obtained
    7. Subject willing to comply with the protocol follow-up requirements
    8. Anticipated life expectancy of at least 3 months
  • EXCLUSION CRITERIA:
    1. Inability to undergo CT-Angiography and/or CT/MR Perfusion imaging (e.g., renal insufficiency, iodine/contrast allergy)
    2. Co-morbid psychiatric or medical illnesses that would confound the neurological assessments
    3. Treatment with tPA beyond 4.5 hours from last known well
    4. Treated with tPA 3‐4.5 hours after last known well AND any of the following:
      • Age >80
      • Current anticoagulant use
      • History of both diabetes AND prior stroke
      • NIHSS >25
      • Ischemic involvement of more than third of the MCA territory
    5. Current participation in another investigational drug or device study.
  • SPECIFIC NEUROIMAGING INCLUSION CRITERIA:
    1. Proven large vessel occlusion in ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial, with or without tandem MCA lesions) determined by MRA or CTA
    2. Large infarct-core lesion on at least one of the following
      • Non-Contrast CT (ASPECTS of 3-5)*,
      • CT perfusion (rCBF<30% ≥50cc),
      • MRI-DWI (ADC<620 ≥50cc),
    3. *ASPECTS 0-2 are not included in this study due to the expected poor outcome in these patients.
  • SPECIFIC NEUROIMAGING EXCLUSION CRITERIA:
    1. Patients who have both ASPECTS of 6-10 on non-contrast CT AND core volume <50 cc on perfusion imaging
    2. Patients with very large core on imaging on non contrast CT i.e. ASPECTS ≤ 2
    3. Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
    4. Significant mass effect with midline shift
    5. Evidence of internal carotid artery dissection that is flow limiting or aortic dissection
    6. Intracranial stent implanted in the same vascular territory that precludes the safe deployment/removal of the neurothrombectomy device
    7. 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).
    8. Signs of established infarct and large area of cerebral edema on non-contrast CT

      ***JUST A REMINDER: WHEN PATIENT’S ARE RANDOMIZED TO THROMBETCTOMY, ADAPT (ASPIRATION ONLY) TECHNIQUES CANNOT BE USED FOR THE FIRST PASS. THE FIRST PASS MUST BE A STENT-RETRIEVER. SUBSEQUENT PASSES CAN BE ASPIRATION ONLY***

SLEEPSMART Nichole

  • 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 Nichole

  • 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

ASPIRE Recruitment VideoMaryLiz

  • 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

SATURN Recruitment VideoMaryLiz

  • 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.

Investigator Initiated Trials

COMETS: Sarah

  • 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: Steph

  • 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

RECAST: Sarah

  • INCLUSION CRITERIA:
    1. Acute ischemic stroke affecting one cerebral hemisphere (i.e. NOT bilateral stroke)
    2. Stroke symptom onset within 72 hours of enrollment
    3. Over 18 years of age
    4. Patients or legally authorized representative (LAR) must be able to read and understand English
    5. Patient or LAR must sign the informed consent form
  • EXCLUSION CRITERIA:
    1. Chronic transcortical stroke
    2. Persistent occlusion of proximal intracranial artery (middle, anterior, or posterior cerebral arteries) which would preclude TCD measurements
    3. Skull defect or skull surgery that will preclude monitoring
    4. Unable or unwilling to remain in bed for 30 minutes of monitoring.

SLAM: Steph

  • 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

CH in LVAD: Sarah

  • INCLUSION CRITERIA:
    1. Advanced heart failure with plan to treat with LVAD
    2. Over 18 years of age
    3. Patients must be able to read and understand English
    4. Patient must sign the informed consent form
  • EXCLUSION CRITERIA:
    1. History of ischemic stroke
    2. History of intracerebral hemorrhage
    3. Known >70% stenosis of the internal carotid artery
    4. Known >70% stenosis of the middle cerebral artery
    5. Skull defect or skull surgery that will preclude monitoring
    6. Unable or unwilling to remain in bed for 30 minutes (to tolerate TCD monitoring)
    7. Unable or unwilling to return for 3-month study visit
    8. INTERMACS profile 1 (critically ill patients requiring temporary assist devices such as ECMO, Impella, aortic balloon pump)

OPTICAL BIOMARKERS of CVD: Sarah

  • HEALTHY SUBJECTS:
    • INCLUSION CRITERIA:
      1. Age 18-49
      2. No history of hypertension, hyperlipidemia, peripheral artery disease, prior stroke, coronary artery disease, chronic kidney disease, congestive heart failure, dementia, or current tobacco use.
    • EXCLUSION CRITERIA:
      1. Hemicraniectomy or other skull defect that would interfere with monitoring. 
      2. Any other illness or condition that the investigator feels would pose a hazard to the subject from participation in the study
      3. Pregnant women* and prisoners are excluded
  • CCOD SUBJECTS:
    • INCLUSION CRITERIA:
      1. Age ≥ 35
      2. Unilateral carotid stenosis or occlusion, defined as any of the following:
        • Carotid ultrasound with a peak systolic velocity >230 cm/s, and either EDV>100 cm/s, or internal to common carotid artery ratio >4.0
        • CT Angiography showing a ≥70% stenosis per NASCET criteria.65
        • MR angiography showing a ≥70% stenosis per NASCET criteria
        • Digital subtraction angiography with a ≥70% stenosis per NASCET criteria
    • EXCLUSION CRITERIA:
      1. Contralateral carotid artery stenosis ≥70% stenosis, using the above definitions
      2. Contralateral carotid artery occlusion
      3. Prior history of carotid territory ischemic stroke or intraparenchymal hemorrhage at any time
      4. History of dementia
      5. Hemicraniectomy or other skull defect that would interfere with monitoring. 
      6. Any other illness or condition that the investigator feels would pose a hazard to the subject from participation in the study
      7. Pregnant women* and prisoners are excluded
  • SVID SUBJECTS:
    • INCLUSION CRITERIA:
      1. Age ≥ 35
      2. Cerebral small vessel disease, defined by:
        • Prior lacunar infarction, <15mm in size and with subcortical location
        • AND
        • Confluent or beginning confluent cerebral white matter hyperintensities, corresponding to Fazekas visual rating scale66 score of 2 or 3 in the periventricular or subcortical white matter on MRI obtained for clinical purposes prior to enrollment.
    • EXCLUSION CRITERIA:
      1. Prior history of intraparenchymal hemorrhage
      2. History of dementia
      3. Hemicraniectomy or other skull defect that would interfere with monitoring. 
      4. Any other illness or condition that the investigator feels would pose a hazard to the subject from participation in the study
      5. Pregnant women* and prisoners are excluded

* Pregnancy Testing: The MRI screening questionnaire will be administered to each patient at the time of check in for the MRI appointment.  The questionnaire will ask each female patient about their “pregnancy” status before each MRI session.  Consistent with clinical care standards, attestation of pregnancy status will be accepted at the time of MRI screening for this study.