Please select the eligibility criteria that correspond to the clinical trial below.
Title: SYNTHESIS: a Randomized Controlled Trial on Intra-arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke. Start up Phase.
Brief Summary: The purpose of this study is to determine whether intra-arterial rt-PA within 6 hours from an ischemic stroke onset, compared with intravenous infusion of the same drug within 3 hours, increases the proportion of independent survivors at 3 months.


Options:
A: Inclusion Criteria:Subjects will be eligible if the following criteria are met:

* Ability to provide written informed consent and comply with study assessments for the full duration of the study.
* Age \> 18 years
* NIHSS ≥ 4 or isolated aphasia or isolated hemianopsia

Exclusion Criteria:

* NIHSS \>30
* Coma
* Rapidly improving symptoms
* History of stroke in the last 6 weeks
* Seizure at onset
* Subarachnoid Hemorrhage (SAH ) or suspected SAH
* Any history of Intracrannial Hemorrhage (ICH)
* Neoplasm
* Septic embolism
* Surgery, biopsy, trauma or LP in last 30 days
* Head trauma in the last 90 days
* Bleeding diathesis, or INR \>1.7 or PTT \>1.5 times baseline or platelet \<100K
* SBP \>180 or DBP ≥100 despite treatment with 3 doses of IV Labetalol (10-20 mg Q10")
* Lacunar stroke syndrome
* CT: Hemorrhage, tumor (except small meningioma), significant mass effect, midline shift, acute hypodensity or \>1/3 MCA territory sulcal effacement
* Radiological contrast hypersensitivity
* Angiographic: Dissection, lack of access, lack of occlusion, or nonatherosclerotic arteriopathy
B: Inclusion Criteria

* Age: 18 through 82 years (i.e., candidates must have had their 18th birthday, but not had their 83rd birthday)
* Initiation of intravenous rt-PA within 3 hours of onset of stroke symptoms. Time of onset is defined as the last time when the subject was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep)
* An NIHSSS \>/= 10 at the time that intravenous rt-PA is begun or an NIHSSS \>7 and \<10 with an occlusion seen in M1, ICA or basilar artery on CTA at institutions where baseline CTA imaging is standard of care for acute stroke patients.
* Investigator verification that the subject has received/ is receiving the correct IV rt-PA dose for the estimated weight prior to randomization

Exclusion Criteria

* History of stroke in the past 3 months
* Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous malformation
* Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal
* Hypertension at time of treatment; systolic BP \> 185 or diastolic \> 110 mm Hg) or aggressive measures to lower BP to below these limits are needed.
* Presumed septic embolus, or suspicion of bacterial endocarditis
* Presumed pericarditis, including pericarditis after acute MI
* Suspicion of aortic dissection
* Recent (within 30 days) surgery or biopsy of parenchymal organ
* Recent (within 30 days) trauma, with internal injuries or ulcerative wounds
* Recent (within 90 days) severe head trauma or head trauma with loss of consciousness
* Any active or recent (within 30 days) hemorrhage
* Pts with known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency or oral anticoagulant therapy require coagulation labs results prior to enrollment. Any subject with INR \> 1.7 or institutionally equivalent prothrombin time is excluded. Patients without history or suspicion of coagulopathy do not require INR or prothrombin time lab results to be available prior to enrollment.
* Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission
* Baseline lab values: glucose \< 50 mg/dl or \> 400 mg/dl, platelets \<100,000, or Hct \<25
* Requires hemodialysis or peritoneal dialysis, or has a contraindication to an angiogram for whatever reason
* Received heparin or a direct thrombin inhibitor (Angiomax, argatroban, Refludan, Pradaxa) within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible
* History of an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days
* History of seizure at onset of stroke
* History of a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be \< 2. This excludes patients who live in a nursing home or who are not fully independent for activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.)
* Other serious, advanced, or terminal illness
* Any other condition that the investigator feels would pose a significant hazard to the subject if Activase (Alteplase) therapy is initiated
* Current participation in another research drug treatment protocol
* Informed consent is not or cannot be obtained.
* High density lesion consistent with hemorrhage of any degree on baseline imaging
* Significant mass effect with midline shift on baseline imaging
* Large (\>1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. (ASPECTS of \< 4 can be used as a guideline) Sulcal effacement and/or loss of grey-white differentiation are not contraindications to tx
* CT evidence of intrapararenchymal tumor
* Baseline CTA without evidence of arterial occlusion
C: Inclusion criteria:

* Sudden focal neurological deficit attributable to a stroke
* Clearly defined time of onset, allowing initiation of intravenous treatment within 3 hours of symptoms onset and intra-arterial treatment within 6 hour of symptoms onset.
* Age between 18 and 80 years

Exclusion criteria:

* Disability preceding stroke consistent with a modified Rankin scale score of 2-4 (see glossary for Rankin scale)
* Coma at onset
* Severe stroke as assessed clinically (e.g. NIHSS\>25)
* Rapidly improving neurological deficit or minor symptoms
* Seizure at onset of stroke
* Clinical presentation suggestive of a subarachnoid hemorrhage (even of CT scan is normal) or condition after subarachnoid hemorrhage from aneurysm
* Previous history of or suspected intracranial hemorrhage
* Previous history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
* Septic embolism, bacterial endocarditis, pericarditis
* Acute pancreatitis
* Arterial puncture at a non compressible site (e.g. subclavian or jugular vein puncture) or traumatic external heart massage or obstetrical delivery within the previous 10 days
* Another stroke or serious head trauma within the preceding 3 months
* Major surgery or significant trauma in past 3 month
* Urinary tract hemorrhage within the previous 21 days
* Documented ulcerative gastrointestinal disease during the last 3 months, esophageal varices, arterial-aneurysm, arterial/venous malformations • Neoplasm with increased bleeding risk
* Severe liver disease, including hepatic failure, cirrhosis, portal hypertension (esophageal varices) and active hepatitis
* Current therapy with intravenous or subcutaneous heparin or oral anticoagulants (e.g. warfarin sodium) to rise the clotting time
* Known hereditary or acquired hemorrhagic diathesis, baseline INR greater than 1.5, aPTT more than 1.5 times normal, or baseline platelet count less than 100,000 per cubic millimeter
* Baseline blood glucose concentrations below 50 mg per deciliter (2.75 mm/L) or above 400 mg per deciliter
* Hemorrhagic retinopathy, e.g. in diabetes (vision disturbances may indicate hemorrhagic retinopathy)
* Any history of prior stroke and concomitant diabetes
* Prior stroke within the last 3 months
* Known contrast sensitivity
* Severe uncontrolled hypertension defined by a blood pressure ≥ 185 mmHg systolic or diastolic ≥ 110 mm Hg in 3 separate occasions at least 10 minutes apart or requiring continuous IV therapy
* Prognosis very poor regardless of therapy; likely to be dead within months.
* Unlikely to be available for follow-up (e.g., no fixed home address, visitor from overseas).Any other condition which local investigators feels would pose a significant hazard in terms of risk/benefit to the patient, or if therapies are impracticable.

Computed tomographic (CT) scan exclusion criteria

* Intracranial tumors except small meningioma
* Hemorrhage of any degree
* Acute infarction (since this may be an indicator that the time of onset is uncorrected
D: Inclusion Criteria:

* Eligible for study treatment within 3-9 hours after onset of stroke symptoms.
* Score of 4-24 on the NIHSS with clinical signs of hemispheric infarction (i.e. hemiparesis) suggestive of ischemic stroke.

Inclusion Criteria from diagnostic imaging screening:

* Distinct penumbra (at least 20%), measured by MRI (PWI/DWI) or perfusion CT, related to middle cerebral artery (MCA), anterior cerebral artery (ACA), or posterior cerebral artery (PCA) territory in a hemispheric distribution.

Exclusion Criteria:

* History or clinical presentation of intracranial hemorrhage (ICH), subarachnoid hemorrhage, arteriovenous malformation, aneurysm, or cerebral neoplasm.
* Rapidly improving neurological symptoms.
* Pre-stroke MRS score of \> 1 (including previous disability).
* Suspected acute vertebral or basilar artery occlusion.
* Current use of anticoagulants and a prolonged prothrombin time.
* Uncontrolled hypertension.
* Baseline hematocrit of \< 0.25.
* Baseline platelet count \< 100,000/mm3.

Answer: C