Please select the eligibility criteria that correspond to the clinical trial below.
Title: Interventional Management of Stroke Trial (IMS III): A Phase III Clinical Trial Examining Whether a Combined Intravenous (IV) and Intra-Arterial (IA) Approach to Recanalization is Superior to Standard IV Rt-PA (Activase®) Alone
Brief Summary: The purpose of this study is to compare two different treatment approaches to recanalization started within 3 hours of symptom onset-combined intravenous (IV) and endovascular therapy and standard intravenous (IV) rt-PA alone.


Options:
A: Inclusion Criteria:

* Female or male inpatients
* Age: 18 - 80 years.
* Clinical diagnosis of ischemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze, vision or neglect. Ischemic stroke is defined as an event characterized by the sudden onset of an acute focal neurologic deficit presumed to be due to cerebral ischemia after CT scan excludes hemorrhage.
* Onset of symptoms between 3 and 4 hours prior to initiation of administration of study drug.
* Stroke symptoms are to be present for at least 30 minutes and have not significantly improved before treatment. Symptoms must be distinguishable from an episode of generalized ischemia (i.e. syncope), seizure, or migraine disorder.
* Patient is willing to participate voluntarily and to sign a written patient informed consent. Informed consent will be obtained from each patient or the subject's legally authorized representative or relatives, or deferred where applicable, according to the regulatory and legal requirements of the participating country.
* Patients who are unable to sign but who are able to understand the meaning of participation in the study may give an oral witnessed informed consent. These patients have to make clear undoubtfully that they are willing to participate voluntarily and must be able to understand an explanation of the contents of he information sheet.
* Willingness and ability to comply with the protocol.

Exclusion Criteria:

* Evidence of intracranial hemorrhage (ICH) on the CT-scan.
* Symptoms of ischaemic attack began more than 4 hours and 30 minutes prior to infusion start or when time of symptom onset is unknown.
* Minor neurological deficit or symptoms rapidly improving before start of infusion.
* Severe stroke as assessed clinically (e.g. NIHSS\>25) and/or by appropriate imaging techniques.
* Epileptic seizure at onset of stroke
* Symptoms suggestive of subarachnoid haemorrhage, even if the CT-scan is normal.
* Administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory
* History of prior stroke and concomitant diabetes. \* Prior stroke within the last 3 months
* Platelet below 100,000/mm3. \* Systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg, or aggressive management (IV medication) necessary to reduce BP to these limits.
* Blood glucose \<50 or \> 400 mg/dl (\< 2.77 or \> 22.15 mmol / l). \* Known haemorraghic diathesis
* Patients receiving oral anticoagulants. \* Manifest or recent severe or dangerous bleeding
* Known history of or suspected intracranial haemorrhage
* Suspected subarachnoid haemorrhage or condition after subarachnoid haemorrhage from aneurysm
* History of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
* Haemorrhagic retinopathy,e.g. in diabetes (vision disturbances may indicate haemorrhagic retinopathy)
* Recent (less than 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel (e.g. subclavian or jugular vein puncture.
* bacterial endocarditis, pericarditis.\* Acute pancreatitis
* Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial- aneurysm, arterial/venous malformation
* Neoplasm with increased bleeding risk
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:

1. Subject or subject's legally authorized representative has signed and dated an Informed Consent Form
2. Age ≥ 18 and \< 85
3. Clinical signs consistent with acute ischemic stroke
4. Thrombolysis in Cerebral Infarction (TICI) 0 or TICI 1 flow in the proximal anterior intracranial vasculature (M1 or M2 of Middle Cerebral Artery (MCA), Internal Carotid Artery (ICA) intracranial, Internal Carotid Artery (ICA) terminal)
5. Presentation within 8 hours of stroke onset according to local stroke protocol
6. If stroke presentation within 4.5 hours, one of these conditions can be met:

   * Bridging protocol (starting intravenous and continuing with intra-arterial) (Up to maximum 0.9 mg/kg)
   * Failed intravenous thrombolysis
   * Direct Intra-arterial treatment (according to institution guidelines)
7. Subject is willing to conduct follow-up visits.
8. National Institutes of Health Stroke Scale (NIHSS) ≥ 8 and ≤ 30
9. Modified Rankin Scale (mRS) ≤ 2 prior to stroke onset

Exclusion Criteria:

1. Females who are pregnant or lactating
2. Known serious sensitivity to radiographic contrast agents
3. Neurological signs that are rapidly improving prior to or at time of treatment
4. Current participation in another investigational drug or device study
5. Life expectancy of less than 90 days
6. National Institutes of Health Stroke Scale (NIHSS) \> 30 or coma
7. Uncontrolled hypertension defined as systolic blood pressure \> 185 or diastolic blood pressure \> 110 that cannot be controlled except with continuous parenteral antihypertensive medication
8. Use of warfarin anticoagulation with International Normalised Ratio (INR) \> 3.0
9. Platelet count \< 30,000
10. Glucose \< 400 mg/dL
11. Previous stroke within 30 days
12. Time of symptom onset unknown
13. Seizure at the onset of stroke
14. Myocardial infarction or infection (sepsis or endocarditis)
15. Arterial tortuosity that would prevent the device from reaching the target vessel
16. Known hypersensitivity to nickel-titanium

    Imaging Exclusion Criteria:
17. Angiographic evidence of carotid dissection, complete cervical carotid occlusions, or vasculitis
18. Stenosis proximal to thrombus site that may preclude safe recovery of the device
19. Brain computed tomography (CT) with signs of hemorrhage, arteriovenous venous malformations, or aneurysm
20. Early ischemic changes greater than 1/3 of the middle cerebral artery (MCA) territory or according to brain computed tomography (CT) Alberta Stroke Program Early CT (ASPECT) score ≤ 6 or according to magnetic resonance diffusion weighted imaging (MR DWI) ASPECT score \<5

Answer: B