Please select the eligibility criteria that correspond to the clinical trial below.
Title: Diffusion Weighted Imaging (DWI) or Computerized Tomography Perfusion (CTP) Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention (DAWN)
Brief Summary: The purpose of the study is to evaluate the hypothesis that Trevo thrombectomy plus medical management leads to superior clinical outcomes at 90 days as compared to medical management alone in appropriately selected subjects experiencing an acute ischemic stroke when treatment is initiated within 6-24 hours after last seen well.


Options:
A: 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
B: Inclusion Criteria:

1. Acute ischemic stroke where patient is ineligible for IV thrombolytic treatment or the treatment is contraindicated (e.g., subject presents beyond recommended time from symptom onset), or where patient has received IV thrombolytic therapy without clinical improvement.
2. No significant pre-stroke functional disability (mRS ≤ 1)
3. Baseline NIHSS score obtained prior to randomization must be equal or higher than 8 points
4. Age ≥18 years
5. Occlusion (TICI 0-1) of the intracranial ICA (distal ICA or T occlusions) and/or MCA-M1 segment suitable for endovascular treatment, as evidenced by CTA, MRA or angiogram, with or without concomitant cervical carotid occlusion or stenosis.
6. Patient treatable within eight hours of symptom onset. Symptoms onset is defined as point in time the patient was last seen well (at baseline). Treatment start is defined as groin puncture.
7. Informed consent obtained from patient or acceptable patient surrogate

Exclusion Criteria:

1. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR \> 3.0
2. Baseline platelet count \< 30.000/µL
3. Baseline blood glucose of \< 50mg/dL or \> 400mg/dl
4. Severe, sustained hypertension (SBP \> 185 mm Hg or DBP \> 110 mm Hg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using AHA guidelines recommended medication (including iv antihypertensive drips), the patient can be enrolled.
5. Patients in coma (NIHSS item of consciousness \>1) (Intubated patients for transfer could be randomized only in case an NIHSS is obtained by a neurologist prior transportation).
6. Seizures at stroke onset which would preclude obtaining a baseline NIHSS
7. Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.
8. History of life threatening allergy (more than rash) to contrast medium
9. Subjects who has received IV t-PA treatment beyond 4,5 hours from the beginning of the symptoms
10. Woman of childbearing potential who is known to be pregnant or lactating or who has a positive pregnancy test on admission.
11. Subject participating in a study involving an investigational drug or device that would impact this study.
12. Cerebral vasculitis
13. Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤1. This excludes patients who are severely demented, require constant assistance in a nursing home type setting or who live at home but are not fully independent in activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.)
14. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas).
15. Hypodensity on CT or restricted diffusion amounting to an ASPECTS score of \<6 on NCCT, or \<5 on DWI MRI. The use of CTP or MRI perfusion is optional.
16. Collaterals with malignant profile on CTA (without colateral circulation on CTA)
17. CT or MR evidence of hemorrhage (the presence of GRE microbleeds is allowed).
18. Significant mass effect with midline shift.
19. Evidence of ipsilateral carotid occlusion, high grade stenosis or arterial dissection in the extracranial or petrous segment of the internal carotid artery that cannot be treated or will prevent access to the intracranial clot or excessive tortuosity of cervical vessels precluding device delivery/deployment
20. Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)
21. Evidence of intracranial tumor (except small meningioma).
C: 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
D: 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

Answer: C