Please select the eligibility criteria that correspond to the clinical trial below.
Title: Basilar Artery International Cooperation Study
Brief Summary: Rationale: Recently our study group reported the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with an acute symptomatic basilar artery occlusion (BAO). Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely. Furthermore, the often-held assumption that intra-arterial thrombolysis (IAT) is superior to intravenous thrombolysis (IVT) in patients with an acute symptomatic BAO is challenged by our data. The BASICS registry was observational and has all the limitations of a non-randomised study. Interpretation of results is hampered by the lack of a standard treatment protocol for all patients who entered the study.

Objective: Evaluate the efficacy and safety of IAT in addition to best medical management (BMM) in patients with basilar artery occlusion.

Study design: Randomised, multi-centre, open label, controlled phase III, treatment trial.

Study population: Patients, aged 18 years and older, with CTA or MRA confirmed basilar occlusion.

Intervention: Patients will be randomised between BMM with additional IAT versus BMM alone. IAT has to be initiated within 6 hours from estimated time of BAO. If treated with as part of BMM, IVT should be started within 4.5 hours of estimated time of BAO.

Main study parameters/endpoints: Favorable outcome at day 90 defined as a modified Rankin Score (mRS - functional scale) of 0-3.


Options:
A: Inclusion Criteria:

* Clinical diagnosis of acute ischemic stroke with unknown symptom onset (e.g. acute wake-up ischemic stroke, acute ischemic stroke with unknown time of symptom onset)
* Last known well without neurological symptoms \>4.5 hours of treatment initiation
* Treatment can be started within 4.5 hours of symptom recognition (e.g. awaking)
* Acute stroke MRI including diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) completed
* Alberta Stroke Program Early CT score (ASPECTS) on initial DWI is 5 or more
* No marked parenchymal hyperintensity visible on FLAIR
* Initial NIHSS ≥2
* Written informed consent by patient or next of kin

Exclusion Criteria:

* Pre-stroke Modified Rankin Scale (mRS) \>1 (patients who have inability to carry out all daily activities and require some help or supervision)
* Contraindications in the Japanese guideline for the intravenous application of recombinant tissue-type plasminogen activator (alteplase)

  * History of nontraumatic intracranial hemorrhage
  * History of stroke within the last 1 month (excluding transient ischemic attack)
  * History of significant head/spinal injury or surgery within the last 3 months
  * History of gastrointestinal or urinary tract bleeding within the last 21 days
  * History of major surgery or significant trauma other than head injury within the last 14 days
  * Hypersensitivity to alteplase
  * Suspected subarachnoid hemorrhage
  * Concurrent acute aortic dissection
  * Concurrent hemorrhage (e.g., intracranial, gastrointestinal, urinary tract, or retroperitoneal, hemoptysis)
  * Systolic blood pressure ≥185 mmHg despite antihypertensive therapy
  * Diastolic blood pressure ≥110 mmhg despite antihypertensive therapy
  * Significant hepatic disorder
  * Acute pancreatitis
  * Blood glucose \<50mg/dL or \>400 mg/dL
  * Platelet count ≤100,000/mm3
  * International normalized ratio of prothrombin time (PT-INR) \>1.7 or Prolonged activated partial thromboplastin time (aPTT: \>1.5 times the baseline value \[\>approximately 40 seconds only as a guide\]) for patients on anticoagulation therapy or those with abnormal coagulation
* Any contraindication to MRI (e.g. cardiac pacemaker)
* Extensive early ischemic change in brain stem or cerebellum (e.g., more than half of brain stem or more than one hemisphere of cerebellum)
* Planned or anticipated treatment with surgery or endovascular reperfusion strategies (e.g., intra-arterial thrombolysis, mechanical recanalization techniques)
* Pregnant, lactating, or potentially pregnant
* Life expectancy 6 months or less by judgment of the investigator
* Inappropriate for study enrollment by judgment of the investigator
B: Inclusion criteria

* Symptoms and signs compatible with ischemia in the basilar artery territory.
* Basilar artery occlusion (BAO) confirmed by CTA or MRA.
* Age 18 years or older (i.e., candidates must have had their 18th birthday).
* If IVT is considered as part of best medical management, IVT should be started within 4.5 hours of estimated time of BAO. (Estimated time of BAO is defined as time of onset of acute symptoms leading to clinical diagnosis of BAO or if not known last time patient was seen normal prior to onset of these symptoms).
* Initiation of IAT should be feasible within 6 hours of estimated time of BAO.

Exclusion criteria

* Pre-existing dependency with mRankin ≥3.
* Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission.
* Patients who require hemodialysis or peritoneal dialysis.
* Other serious, advanced, or terminal illness.
* Any other condition that the investigator feels would pose a significant hazard to the patient if thrombolytic therapy is initiated.
* Current participation in another research drug treatment protocol (patient cannot start another experimental agent until after 90 days).
* Informed consent is not or cannot be obtained.

Imaging exclusion criteria

* High-density lesion consistent with hemorrhage of any degree.
* Significant cerebellar mass effect or acute hydrocephalus.
* Bilateral extended brainstem ischemia.
C: 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
D: General Inclusion Criteria:

1. Clinical signs and symptoms consistent with the diagnosis of an acute ischemic stroke, and subject belongs to one of the following subgroups:

   1. Subject has failed IV t-PA therapy (defined as a confirmed persistent occlusion 60 min after administration)
   2. Subject is contraindicated for IV t-PA administration
2. Age ≥18
3. Baseline NIHSS ≥10 (assessed within one hour of measuring core infarct volume)
4. Subject can be randomized between with 6 to 24 hours after time last known well
5. No significant pre-stroke disability (pre-stroke mRS must be 0 or 1)
6. Anticipated life expectancy of at least 6 months
7. Subject willing/able to return for protocol required follow up visits
8. Subject or subject's Legally Authorized Representative (LAR) has signed the study Informed Consent form\*

   * If approved by local ethics committee and country regulations, the investigator is allowed to enroll a patient utilizing emergency informed consent procedures if neither the patient nor the representative or person of trust is available to sign the informed consent form. However, as soon as possible, the patient is informed and his/her consent is requested for the possible continuation of this research. (Not applicable to U.S. Sites.)

Imaging Inclusion Criteria:

1. \< 1/3 MCA territory involved, as evidenced by CT or MRI
2. Occlusion of the intracranial ICA and/or MCA-M1 as evidenced by MRA or CTA
3. Clinical Imaging Mismatch (CIM) defined as one of the following on MR-DWI or CTP-rCBF maps:

   1. 0-\<21 cc core infarct and NIHSS ≥ 10 (and age ≥ 80 years old)
   2. 0-\<31 cc core infarct and NIHSS ≥ 10 (and age \< 80 years old)
   3. 31 cc to \<51 cc core infarct and NIHSS ≥ 20 (and age \< 80 years old)

General Exclusion Criteria:

1. History of severe head injury within past 90 days with residual neurological deficit, as determined by medical history
2. Rapid improvement in neurological status to an NIHSS \<10 or evidence of vessel recanalization prior to randomization
3. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor (e.g. Aricept)
4. Seizures at stroke onset if it makes the diagnosis of stroke doubtful and precludes obtaining an accurate baseline NIHSS assessment
5. Baseline blood glucose of \<50mg/dL (2.78 mmol) or \>400mg/dL (22.20 mmol)
6. Baseline hemoglobin counts of \<7 mmol/L
7. Baseline platelet count \< 50,000/uL
8. Abnormal baseline electrolyte parameters as defined by sodium concentration \<130 mmol/L, potassium concentration \<3 mEq/L or \>6 mEq/L
9. Renal failure as defined by a serum creatinine \>3.0 mg/dL (264 µmol/L) NOTE: subjects on renal dialysis may be treated regardless of serum creatinine levels
10. Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with INR \> 3.0 or PTT \> 3 times normal. Patients on factor Xa inhibitor for 24-48 hours ago must have a normal PTT.
11. Any active or recent hemorrhage within the past 30 days
12. History of severe allergy (more than rash) to contrast medium
13. Severe, sustained hypertension (Systolic Blood Pressure \>185 mmHg or Diastolic Blood Pressure \>110 mmHg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using medication the subject can be enrolled
14. Female who is pregnant or lactating at time of admission
15. Current participation in another investigational drug or device study
16. Presumed septic embolus, or suspicion of bacterial endocarditis
17. Treatment with any cleared thrombectomy devices or other intra-arterial (neurovascular) therapies prior to randomization

Imaging Exclusion Criteria:

1. Evidence of intracranial hemorrhage on CT/MRI
2. CTA or MRA evidence of flow limiting carotid dissection, high-grade stenosis, or complete cervical carotid occlusion requiring stenting at the time of the index procedure (i.e., mechanical thrombectomy).
3. Excessive tortuosity of cervical vessels on CTA/MRA that would likely preclude device delivery/deployment
4. Suspected cerebral vasculitis based on medical history and CTA/MRA
5. Suspected aortic dissection based on medical history and CTA/MRA
6. Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the Trevo device
7. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior circulation/vertebrobasilar system) as confirmed on CTA/MRA, or clinical evidence of bilateral strokes or strokes in multiple territories
8. Significant mass effect with midline shift as confirmed on CT/MRI
9. Evidence of intracranial tumor (except small meningioma) as confirmed on CT/MRI

Answer: B