Clinical trial NCT01745692: Pragmatic Ischaemic Stroke Thrombectomy Evaluation
Official 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Ischaemic Stroke
Lead sponsor: NHS Greater Glasgow and Clyde
Sponsor class: OTHER
Collaborators: name: University of Glasgow
name: University of Edinburgh
name: Newcastle University
First posted: 2012-12-10
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: modified Rankin Scale
timeFrame: Day 90 +/-7
Secondary outcomes:
measure: modified Rankin Scale
timeFrame: Day 90+/-7
measure: Mortality
timeFrame: Day 90 +/-7
measure: modified Rankin Scale
timeFrame: Day 90 +/-7
measure: NIH Stroke Scale (NIHSS)
timeFrame: 72 hours
measure: Angiographic patency
timeFrame: 22-36 hours
measure: Immediate recanalisation rate
timeFrame: End of procedure
measure: Home Time
timeFrame: Day 90 +/-7
measure: Symptomatic intracranial haemorrhage
timeFrame: 22-26h
measure: Intracranial haemorrhage
timeFrame: 22-36 hours
measure: Significant extracranial bleeding
timeFrame: Up to day 90
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
Study officials:
affiliation: University of Glasgow
name: Keith W Muir, MD, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heggie R, Wu O, White P, Ford GA, Wardlaw J, Brown MM, Clifton A, Muir KW. Mechanical thrombectomy in patients with acute ischemic stroke: A cost-effectiveness and value of implementation analysis. Int J Stroke. 2020 Oct;15(8):881-898. doi: 10.1177/1747493019879656. Epub 2019 Sep 30.
citation: Muir KW, Ford GA, Messow CM, Ford I, Murray A, Clifton A, Brown MM, Madigan J, Lenthall R, Robertson F, Dixit A, Cloud GC, Wardlaw J, Freeman J, White P; PISTE Investigators. Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial. J Neurol Neurosurg Psychiatry. 2017 Jan;88(1):38-44. doi: 10.1136/jnnp-2016-314117. Epub 2016 Oct 18.
citation: Hurford R, Tyrrell PJ. Stroke thrombolysis: where are we and where are we going? Clin Med (Lond). 2013 Dec;13 Suppl 6:s20-3. doi: 10.7861/clinmedicine.13-6-s20.