Please select the eligibility criteria that correspond to the clinical trial below.
Title: An International Randomised Controlled Trial to Establish the Effects of Low-dose rtPA and the Effects of Early Intensive Blood Pressure Lowering in Patients With Acute Ischaemic Stroke
Brief Summary: ENCHANTED is an independent, investigator initiated, international collaborative, quasi-factorial randomised controlled trial involving a package of 2 linked comparative randomised treatment arms, which aims to address 4 key questions in patients eligible for thrombolysis in the acute phase of ischaemic stroke. (1) Does low-dose (0.6 mg/kg) intravenous (i.v.) recombinant tissue plasminogen activator (rtPA) provide equivalent benefits compared to standard-dose (0.9 mg/kg) rtPA? (2) Does intensive blood pressure (BP) lowering (130-140 mmHg systolic target) improve outcomes compared to the current guideline recommended level of BP control (180 mmHg systolic target)? (3) Does low-dose (0.6 mg/kg) intravenous (i.v.) recombinant tissue plasminogen activator (rtPA) reduce the risk of symptomatic intracerebral haemorrhage (sICH)? (4) Does the addition of intensive BP lowering to thrombolysis with rtPA reduce the risk of any intracerebral haemorrhage (ICH)?

The rtPA dose arm of the study addressing questions (1) and (3) concluded with a publication of the results in May 2016. The BP intensity arm of the study addressing questions (2) and (4) concluded with a publication of the results in February 2019.


Options:
A: Inclusion criteria

* Symptoms and signs compatible with ischemia in the basilar artery territory.
* Basilar artery occlusion (BAO) confirmed by CTA or MRA.
* Age 18 years or older (i.e., candidates must have had their 18th birthday).
* If IVT is considered as part of best medical management, IVT should be started within 4.5 hours of estimated time of BAO. (Estimated time of BAO is defined as time of onset of acute symptoms leading to clinical diagnosis of BAO or if not known last time patient was seen normal prior to onset of these symptoms).
* Initiation of IAT should be feasible within 6 hours of estimated time of BAO.

Exclusion criteria

* Pre-existing dependency with mRankin ≥3.
* Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission.
* Patients who require hemodialysis or peritoneal dialysis.
* Other serious, advanced, or terminal illness.
* Any other condition that the investigator feels would pose a significant hazard to the patient if thrombolytic therapy is initiated.
* Current participation in another research drug treatment protocol (patient cannot start another experimental agent until after 90 days).
* Informed consent is not or cannot be obtained.

Imaging exclusion criteria

* High-density lesion consistent with hemorrhage of any degree.
* Significant cerebellar mass effect or acute hydrocephalus.
* Bilateral extended brainstem ischemia.
B: Inclusion Criteria:

* Intracranial Occlusion of internal carotid arteries and/or proximal middle cerebral (segment M1) diagnosis made on initial Imaging.
* Reperfusion after a thrombectomy procedure (defined by a 2b-3 TICI score -Thrombolysis In Cerebral Infarction- score).

Exclusion Criteria:

* Per-procedure hemorrhagic complications (prior to reperfusion)
* Systolic blood pressure at baseline \<130 mm Hg within one hour of recanalization
* Pre-existing stroke handicap defined by a Rankin score (modified scale, mRS)\> 3
* Hemodynamically significant carotid stenosis
* Occlusion of the isolated cervical carotid artery
* Known pregnancy
* Legal protection
* Non-affiliation to a social security scheme
* Refusal of the patient (or of his / her relatives in case of urgent inclusion)
C: 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.
D: 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.

Answer: D