Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised Controlled Clinical Trial of Adjunctive Mechanical Thrombectomy Compared With Intravenous Thrombolysis in Patients With Acute Ischaemic Stroke Due to an Occluded Major Intracranial Vessel.
Brief Summary: Ischaemic strokes (those caused by blockage in an artery in the brain caused by a blood clot) can be treated with very early use of clot-busting (thrombolytic) drugs to attempt to restore the blood supply and limit the damage, resulting in an increased proportion of people making a recovery to independence after stroke. However, drug treatment only succeed in restoring blood flow in a minority of people with clots in the larger arteries (10-25% depending on the size of the blood vessel) and these people also have the most severe strokes and highest risk of death or dependence as a result of the stroke. Current best treatment is therefore least effective in the group with the most severe strokes. Devices that can be fed through the blood vessels to either remove or break up the blood clot in the brain vessels can open this type of large artery blockage. However, using these devices is a highly skilled procedure and it takes some time both to set up the necessary facilities (including anaesthetic, nurses and medical support) and to reach the blockage. The extra time that is required to use these devices may mean that brain tissue is already irreversibly damaged. If so, then an individual patient cannot benefit and indeed may be harmed by opening the artery. There are no completed clinical trials comparing the outcome in people treated with standard stroke treatment and those treated with devices. PISTE is a randomised, controlled trial to test whether additional mechanical thrombectomy device treatment improves functional outcome in patients with large artery occlusion who are given IV thrombolytic drug treatment as standard care.


Options:
A: 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).
B: Inclusion Criteria:

1. Age 18 - 80
2. Clinical signs consistent with acute ischemic stroke
3. Prestroke Modified Rankin Score ≤ 1
4. NIHSS ≥ 8 and \< 30 at the time of randomization
5. Initiation of IV t-PA within 4.5 hours of onset of stroke symptoms (onset time is defined as the last time when the patient was witnessed to be at baseline), with investigator verification that the subject has received / is receiving the correct IV t-PA dose for the estimated weight prior to randomization.
6. Thrombolysis in Cerebral Infarction (TICI) 0-1 flow in the intracranial internal carotid artery, M1 segment of the MCA, or carotid terminus confirmed by CT or MR angiography that is accessible to the Solitaire™ FR Device.
7. Subject is able to be treated within 6 hours of onset of stroke symptoms and within 1.5 hours (90 minutes) from CTA or MRA to groin puncture.
8. Subject is willing to conduct protocol-required follow-up visits.
9. An appropriate signed and dated Informed Consent Form (as allowed according to country regulations and approved by ethics committee and/or IRB) has been obtained
10. Subject is affiliated with a social security system (if required by individual country regulations).
11. Subject meets national regulatory criteria for clinical trial participation.

Exclusion Criteria:

1. Subject who is contraindicated to IV t-PA as per local national guidelines.
2. Female who is pregnant or lactating or has a positive pregnancy test at time of admission.
3. As applicable by French law, subject who is a protected individual such as an incompetent adult or incarcerated person.
4. Rapid neurological improvement prior to study randomization suggesting resolution of signs/symptoms of stroke.
5. Known serious sensitivity to radiographic contrast agents.
6. Known sensitivity to Nickel, Titanium metals or their alloys.
7. Current participation in another investigational drug or device treatment study.
8. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency. (A subject without history or suspicion of coagulopathy does not require INR or prothrombin time lab results to be available prior to enrollment.)
9. Renal Failure as defined by a serum creatinine \> 2.0 mg/dl (or 176.8 μmol/l) or Glomerular Filtration Rate \[GFR\] \< 30Warfarin therapy with INR greater than 1.7.
10. Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason
11. Life expectancy of less than 90 days.
12. Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal.
13. Suspicion of aortic dissection.
14. Subject with a co-morbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments.
15. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol (defined as regular or daily consumption of more than 4 alcoholic drinks per day).
16. Known history of arterial tortuosity, pre-existing stent, and/or other arterial disease which would prevent the device from reaching the target vessel and/or preclude safe recovery of the device.

Imaging Exclusion Criteria:

1. Computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of hemorrhage on presentation.
2. CT or MRI evidence of mass effect or intra-cranial tumor (except small meningioma).
3. CT or MRI evidence of cerebral vasculitis.
4. CT showing hypodensity or MRI showing hyperintensity involving greater than 1/3 of the middle cerebral artery (MCA) territory (or in other territories, \>100 cc of tissue) on presentation.
5. Baseline non-contrast CT or DWI MRI evidence of a moderate/large core defined as extensive early ischemic changes of Alberta Stroke Program Early CT score (ASPECTS) \< 6.
6. CT or MRI evidence of a basilar artery (BA) occlusion or posterior cerebral artery (PCA) occlusion.
7. CTA or MRA evidence of carotid dissection or complete cervical carotid occlusion requiring stenting at the time of the index procedure (i.e., mechanical thrombectomy)
8. Imaging evidence that suggests, in the opinion of the investigator, the subject is not appropriate for mechanical thrombectomy intervention (e.g., inability to navigate to target lesion, moderate/large infarct with poor collateral circulation, etc).
C: 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 recanalization after a minimum of 30 min from start of iv tPA infusion
* 2. No significant pre-stroke functional disability (mRS ≤ 1)
* 3. Baseline NIHSS score obtained prior to randomization must be equal or higher than 6 points
* 4. Age ≥18 and ≤ 85.
* 5. Occlusion (TICI 0-1) of the intracranial ICA (distal ICA or T occlusions), MCA-M1 segment or tandem proximal ICA/MCA-M1 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:

* Clinical 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)
* 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. Renal insufficiency with creatinine ≥ 3 mg/dl
* 11. Woman of childbearing potential who is known to be pregnant or lactating or who has a positive pregnancy test on admission.
* 12. Subject participating in a study involving an investigational drug or device that would impact this study.
* 13. Cerebral vasculitis
* 14. 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.)
* 15. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas).

Neuroimaging criteria:

* 16. Hypodensity on CT or restricted diffusion amounting to an ASPECTS score of \<7 on NCCT or \<6 on DWI MRI. Patients 81 to 85 years old with ASPECTS score on non-contrast CT or DWI MRI \<9 must be excluded. ASPECTS must be evaluated by CBV maps of CT Perfusion, CTA source imaging (CTA-SI) or DWI-MR in patients whose vascular occlusion study (CTA/MRA) confirming qualifying occlusion, is performed beyond 4.5 hours of last seen well.
* 17. CT or MR evidence of hemorrhage (the presence of 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).
D: Inclusion Criteria:

* Clinical diagnosis of supratentorial acute ischaemic stroke
* Male or nonpregnant female ≥18 years of age
* Clinically significant neurological deficit and NIHSS score ≥6.
* Eligible for IV rtPA according to standard guidelines and able to be commenced on IV treatment \<4.5h after symptom onset.
* Enrolment, randomisation and procedure commencement (groin puncture) possible within 90 minutes of the start of IV rtPA treatment (groin puncture maximum 5.5h after stroke onset).
* Occlusion of the main middle cerebral artery (MCA) trunk, MCA bifurcation or intracranial internal carotid artery(carotidT, M1 or single proximal M2 branch) demonstrated on CTA, MRA, or DSA.
* Interventional device delivery (guide catheter placed beyond aortic arch and angio obtained) can be achieved within 6 hours of onset of the stroke.
* Consent of patient or representative.
* Independent prior to the stroke (estimated mRS 02)
* Expected to be able to be followed up at 3 months

Exclusion Criteria:

* CT evidence of intracranial haemorrhage, or evidence of extensive established hypodensity on CT.
* Clinical history suggestive of subarachnoid haemorrhage even if CT normal.
* Known vascular access contraindications e.g. femoral bypass surgery, tight ipsilateral carotid stenosis, unsuitable proximal vascular anatomy likely to render endovascular catheterisation difficult or impossible.
* Extracranial ICA occlusion or basilar artery occlusion
* Alternative intracranial pathology potentially responsible for the new symptoms
* Medical comorbidities which would preclude safe cerebral vessel catheterisation or which are expected to limit life expectancy to \<3 months (eg severe cardiac, renal or hepatic failure, significant coagulopathy, metastatic malignancy)
* Known allergy to radiological contrast

Answer: D