Please select the eligibility criteria that correspond to the clinical trial below.
Title: POSITIVE: PerfusiOn Imaging Selection of Ischemic STroke PatIents for EndoVascular ThErapy
Brief Summary: Primary Endpoint:

The primary objective is to show that AIS patients, ineligible for or refractory to treatment with IV-tPA, with appropriate image selection, treated with mechanical thrombectomy within 6-12 hours of symptom onset have less stroke related disability and improved good functional outcomes as compared to those treated with best MT with respect to endpoint defined as:

• 90-day global disability assessed via the modified Rankin score (mRS), analyzed using raw mRS scores. Statistical details can be found in section 7.2.

Secondary Endpoints:

* 90-day global disability in the 6-12 hr cohort assessed via the overall distribution of mRS
* Proportion of patients with good functional recovery for the 6-12 hr cohort as defined by mRS 0-2 at 90 days
* Mortality at 30 and 90 days
* Intracranial hemorrhage with neurological deterioration (NIHSS worsening \>4) within 24 hours of randomization
* Procedure related serious adverse events (SAE's)
* Arterial revascularization measured by TICI 2b or 3 following device use


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:

* Acute ischemic stroke patients who were treated with intravenous rt-PA therapy within 4.5 hours from onset and have persistent occlusion of IC and M1 proximal portion\* confirmed by cerebral angiography.

  \*: M1 proximal portion means the segment of MCA within 5mm from the internal carotid bifurcation.
* Patients who can receive endovascular treatment within 8 hours after the onset.
* Patients whose DWI-ASPECTS was 5 points and more, or CT-ASPECT was 6 points and more just before cerebral angiography.
* Patients whose NIHSS is between 8 and 29 points.
* Patients who are between 20 and 85 years.
* Gender does not matter.
* Consent of this study participants must be obtained from patients or legal representative in writing.

Exclusion Criteria:

* Patients whose neurological symptoms improved and NIHSS is eight points and less after intravenous rt-PA therapy.
* Patients whose mRS was 3 points and more before the onset. 3)Patients with past history of lumbar puncture or arterial puncture that were difficult of hemostasis.
* Patients with intracranial tumor
* Patients with hypersensitivity to contrast agent.
* Patients with serious renal disease.
* Patients with malignant tumor.
* Patients with pregnancy or suspect of pregnancy, or during lactation.
* Patients with findings of acute myocardial infarction or pericarditis after myocardial infarction.
* Patients who cannot be followed for 3 months.
* Patients with past history of cerebral aneurysm, cerebral arteriovenous malformation, cerebral venous thrombosis, or moyamoya disease.
* Patients with other occlusions besides ICA or M1 proximal portion.
* Patients with aortic dissection complicating endovascular treatment.
* Patients with tortuous arteries that prevent the navigation of the device to the target vessel.
* Patients considered inappropriate to participate in the study.
C: Inclusion Criteria:

* Adult (age ≥18 years)
* A clinical diagnosis of acute ischaemic stroke confirmed by brain imaging
* Able to receive treatment within 4.5 hours after the definite time of onset of symptoms
* Have a systolic BP ≤185 mmHg
* Provide informed consent (or via an appropriate proxy, according to local requirements)

Specific criteria for arm \[A\] of low-dose vs standard-dose rtPA (Recruitment completed in August 2015.):

* Able to receive either low-dose or standard-dose rtPA

Specific criteria for arm \[B\] of intensive BP lowering vs guideline recommended BP control

* Patient will or has received thrombolysis treatment with rtPA, either randomised dose within the trial or physician decided dose rtPA outside of the trial
* Sustained elevated systolic BP level, defined as 2 readings ≥ 150 mmHg
* Able to commence intensive BP lowering treatment within 6 hours of stroke onset
* Able to receive either immediate intensive BP lowering or conservative BP management

Exclusion Criteria:

* Unlikely to potentially benefit from the therapy (e.g. advanced dementia), or a very high likelihood of death within 24 hours of stroke onset.
* Other medical illness that interferes with outcome assessments and follow-up \[known significant pre-stroke disability (mRS scores 2-5)\].
* Specific contraindications to rtPA (Actilyse) or any of the blood pressure agents to be used.
* Participation in another clinical trial involving evaluation of pharmacological agents.
* Need for following concomitant medication, including phosphodiesterase inhibitors and monoamine oxidase inhibitors.
D: 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

Answer: D