Please select the eligibility criteria that correspond to the clinical trial below.
Title: Parallel Group, Randomized Clinical Trial of Direct Intra-arterial Thrombectomy Versus Intravenous Thrombolysis With Intra-arterial Thrombectomy for Patients With Large Vessel Occlusion of the Anterior Circulation
Brief Summary: Background: Intravenous thrombolysis (IVT) combined with mechanical thrombectomy (MT) has been proven safe and effective in patients with acute ischemic stroke (AIS) of anterior circulation large vessel occlusion (LVO). Despite recanalization, a considerable proportion of patients do not recover. The incidence of symptomatic intracerebral hemorrhage (sICH) was similar between combined IVT plus MT and IVT, suggesting that this complication could not be attributed to the MT, but rather to pre-treatment with IVT. Meanwhile, the incidence of intracranial atherosclerosis stenosis (ICAS) is higher in Asians. It is not clear whether patients with ICAS benefit from pretreatment with alteplase or not and how ICAS modifies treatment effect.

Objective: To assess whether direct MT is non-inferior compared to combined IVT plus MT in patients with AIS due to an anterior circulation LVO, and to assess treatment effect modification by presence of ICAD.

Study design: This is a parallel group, RCT of direct MT compared to combined IVT plus MT, using a non-inferiority design. The trial has observer blinded assessment of the primary outcome and of neuro-imaging at baseline and follow up. The trial will be executed in collaboration with MRCLEAN NO-IV investigators.

Study population: Patients with AIS of anterior circulation VLO confirmed by CTA. Initiation of IVT must be feasible within 4.5 hours from symptom onset. Age must be 18 or over and NIHSS 2 or more.

Main outcomes: The full distribution of the mRS at 3 months. Secondary outcomes: 1. death within 90 +/- 14 days; 2. pre-interventional reperfusion assessed on first intracranial DSA; 3. eTICI19 score on final angiography of MT; 4. score on the NIHSS at 24 +/- 6 hours and 5-7 days, or at discharge; 5. recanalization rate at 24-72h by CTA; 6. Final lesion volume at 5-7 days on NCCT20; 7. score on the EuroQoL 5-dimensions 5-level (EQ5D-5L)21 and Barthel index22 at 90 +/- 14 days; 8. dichotomous clinical outcome on the mRS at 90 +/- 14 days.


Options:
A: Inclusion Criteria:

* Age \> 18 years with no upper age limit.
* Cerebral infarction in the anterior circulation
* Occlusion of the anterior circulation proven by CT angiography or MR angiography
* With or without previous Intravenous thrombolysis
* Start of thrombectomy procedure within 6 hours of symptoms onset.
* Patient expresses verbally his non-opposition to be enrolled in the study ; in case patient cannot communicate, verbal non-opposition is obtained from his close / trusted person

Exclusion Criteria:

* Absence of indication for thrombectomy
* Cons-indication for thrombectomy
* Presence of cerebral infarction of the posterior circulation
* Occlusion of the cervical carotid artery
* Allergy to x-ray contrast products
* Patient was bedridden or using a wheelchair most of the day (pre-event modified Rankin Scale score \> 3) prior to stroke
* Pregnancy or breastfeeding
* Patient under legal protection
* No affiliation to health insurance

Secondary exclusion criteria

- Lack of access route for catheterization
B: 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 hours of when groin puncture can be obtained
4. Neuroimaging demonstrates large vessel proximal occlusion (distal ICA through MCA bifurcation)
5. The operator feels that the stroke can be appropriately treated with traditional endovascular approaches (the ADAPT approach or conventional first-line stent retriever approach)
6. Pre-event Modified Rankin Scale score 0-1
7. Non-contrast CT/CTA for trial eligibility performed or repeated at treating ADAPT stroke center.
8. Consenting requirements met according to local IRB

Exclusion Criteria:

1. Patient is more than 6-hours from symptom onset
2. Rapidly improving neurologic examination
3. Absence of large vessel occlusion on non-invasive imaging
4. Presence of an existing or pre-existing large territory infarction
5. Known or suspected pre-existing (chronic) large vessel occlusion in the symptomatic territory
6. Absent femoral pulses
7. Excessive vascular access tortuosity that will likely result in unstable access platform.
8. Pregnancy; if a woman is of child-bearing potential a urine or serum beta HCG test is positive.
9. Severe contrast allergy or absolute contraindication to iodinated contrast.
10. Clinical history, past imaging or clinical judgment suggests that the intracranial occlusion is chronic.
11. Patient has a severe or fatal comorbidities that will likely prevent improvement or follow-up or that will render the procedure unlikely to benefit the patient.

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
* Core infarct lesion volume \>50 cc.
* 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.
C: 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).
D: Inclusion Criteria:

* a clinical diagnosis of acute ischemic stroke,
* caused by a large vessel occlusion of the anterior circulation (distal intracranial carotid artery or middle M1/proximal M2) cerebral artery confirmed by CTA,
* CT or MRI ruling out intracranial hemorrhage,
* eligible for IVT and IAT (within 4.5 hours after symptom onset),
* a score of at least 2 on the NIH Stroke Scale,
* age of 18 years or older,
* written informed consent.

Exclusion Criteria:

* - Pre-stroke disability which interferes with the assessment of functional outcome at 90 days, i.e. mRS \>2
* Any contra-indication for IVT, according to guidelines of the American Heart Association, i.e.:

  * arterial blood pressure exceeding 185/110 mmHg
  * blood glucose less than 2.7 or over 22.2 mmol/L
  * cerebral infarction in the previous 6 weeks with residual neurological deficit or signs of recent infarction on neuro-imaging
  * serious head trauma in the previous 3 months
  * major surgery or serious trauma in the previous 2 weeks
  * gastrointestinal or urinary tract hemorrhage in the previous 3 weeks
  * previous intracerebral hemorrhage
  * use of anticoagulant with INR exceeding 1.7
  * known thrombocyte count less than 100 x 109/L
  * treatment with direct thrombin or factor X inhibitors
  * treatment with heparin (APTT exceeds the upper limit of normal value) in the previous 48 hours.

Answer: D