Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE)

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.

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.

Study Overview

• Status: Terminated
• Conditions: Acute Ischaemic Stroke
• Intervention / Treatment: Drug: Intravenous rtPA; Device: Mechanical thrombectomy

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • NHS Greater Glasgow and Clyde

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravenous rtPA; IV alteplase (rtPA) 0.9mg/kg (10% of dose as bolus followed by 90% as infusion over 1 hour, to a maximum dose of 90mg total) given within 4.5 hours of onset of stroke symptoms	Drug: Intravenous rtPA; All patients receive IV alteplase; Other Names: alteplase
Experimental: Intravenous rtPA and Mechanical Thrombectomy; IV alteplase (rtPA) 0.9mg/kg (10% of dose as bolus followed by 90% as infusion over 1 hour, to a maximum dose of 90mg total) given within 4.5 hours of onset of stroke symptoms + additional mechanical thrombectomy procedure to commence within 90 minutes of start of IV rtPA infusion	Drug: Intravenous rtPA; All patients receive IV alteplase; Other Names: alteplase; Device: Mechanical thrombectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale	The proportion with favourable functional outcome defined as mRS 0-2 at 90 (+/-7) days based on the modified Rankin scale structured interview	Day 90 +/-7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale	Full neurological recovery (mRS 0-1 versus 2-6)	Day 90+/-7
Mortality		Day 90 +/-7
modified Rankin Scale	Change in distribution of mRS scores adjusted for baseline variables	Day 90 +/-7
NIH Stroke Scale (NIHSS)	Early major neurological improvement of 8 or more points, or return to NIHSS total score of 0 or 1, at 72 hours (or discharge if earlier)	72 hours
Angiographic patency	Angiographic patency at 22-36 hours (Core lab assessed), using CTA or MRA	22-36 hours
Immediate recanalisation rate	Immediate (i.e. end of procedure) recanalisation rates in subjects undergoing interventional procedures (core lab assessed).	End of procedure
Home Time	Days spent at home between stroke and day 90	Day 90 +/-7
Symptomatic intracranial haemorrhage	Symptomatic intracranial haemorrhage rates defined as local or remote parenchymal haemorrhage type 2 (PH2 or PHr2 ICH by ECASS 2 definition) on the 22-36 h post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 h, or leading to death (SITS-MOST definition)	22-26h
Intracranial haemorrhage	Any intracranial haemorrhage on 22-36h CT or MRI	22-36 hours
Significant extracranial bleeding	Extracranial bleeding, groin haematoma requiring evacuation / surgery or transfusion	Up to day 90

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Edinburgh; Newcastle University; University of Glasgow
• Investigators: Principal Investigator: Keith W Muir, MD, FRCP, University of Glasgow

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: November 30, 2012
• First Submitted That Met QC Criteria: December 7, 2012
• First Posted (Estimate): December 10, 2012

Study Record Updates

• Last Update Posted (Estimate): October 26, 2015
• Last Update Submitted That Met QC Criteria: October 23, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: GN11NE257; TSA 2011/06 (Other Grant/Funding Number: The Stroke Association)