Back to resultsPragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE)
Primary Purpose
Acute Ischaemic Stroke
Status
Terminated
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Mechanical thrombectomy
Intravenous rtPA
Sponsored by
About this trial
This is an interventional treatment trial for Acute Ischaemic Stroke
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
Sites / Locations
- NHS Greater Glasgow and Clyde
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Intravenous rtPA
Intravenous rtPA and Mechanical Thrombectomy
Arm Description
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
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
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
modified Rankin Scale
Full neurological recovery (mRS 0-1 versus 2-6)
Mortality
modified Rankin Scale
Change in distribution of mRS scores adjusted for baseline variables
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)
Angiographic patency
Angiographic patency at 22-36 hours (Core lab assessed), using CTA or MRA
Immediate recanalisation rate
Immediate (i.e. end of procedure) recanalisation rates in subjects undergoing interventional procedures (core lab assessed).
Home Time
Days spent at home between stroke and day 90
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)
Intracranial haemorrhage
Any intracranial haemorrhage on 22-36h CT or MRI
Significant extracranial bleeding
Extracranial bleeding, groin haematoma requiring evacuation / surgery or transfusion
Full Information
NCT ID
NCT01745692
First Posted
November 30, 2012
Last Updated
October 23, 2015
Sponsor
NHS Greater Glasgow and Clyde
Collaborators
University of Glasgow, University of Edinburgh, Newcastle University
1. Study Identification
Unique Protocol Identification Number
NCT01745692
Brief Title
Pragmatic Ischaemic Stroke Thrombectomy Evaluation
Acronym
PISTE
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
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Terminated
Why Stopped
IDMC decision - recommended on basis of results from other relevant clinical trials, there were not safety concerns
Study Start Date
December 2012 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NHS Greater Glasgow and Clyde
Collaborators
University of Glasgow, University of Edinburgh, Newcastle University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischaemic Stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intravenous rtPA
Arm Type
Active Comparator
Arm Description
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
Arm Title
Intravenous rtPA and Mechanical Thrombectomy
Arm Type
Experimental
Arm Description
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
Intervention Type
Device
Intervention Name(s)
Mechanical thrombectomy
Intervention Type
Drug
Intervention Name(s)
Intravenous rtPA
Other Intervention Name(s)
alteplase
Intervention Description
All patients receive IV alteplase
Primary Outcome Measure Information:
Title
modified Rankin Scale
Description
The proportion with favourable functional outcome defined as mRS 0-2 at 90 (+/-7) days based on the modified Rankin scale structured interview
Time Frame
Day 90 +/-7
Secondary Outcome Measure Information:
Title
modified Rankin Scale
Description
Full neurological recovery (mRS 0-1 versus 2-6)
Time Frame
Day 90+/-7
Title
Mortality
Time Frame
Day 90 +/-7
Title
modified Rankin Scale
Description
Change in distribution of mRS scores adjusted for baseline variables
Time Frame
Day 90 +/-7
Title
NIH Stroke Scale (NIHSS)
Description
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)
Time Frame
72 hours
Title
Angiographic patency
Description
Angiographic patency at 22-36 hours (Core lab assessed), using CTA or MRA
Time Frame
22-36 hours
Title
Immediate recanalisation rate
Description
Immediate (i.e. end of procedure) recanalisation rates in subjects undergoing interventional procedures (core lab assessed).
Time Frame
End of procedure
Title
Home Time
Description
Days spent at home between stroke and day 90
Time Frame
Day 90 +/-7
Title
Symptomatic intracranial haemorrhage
Description
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)
Time Frame
22-26h
Title
Intracranial haemorrhage
Description
Any intracranial haemorrhage on 22-36h CT or MRI
Time Frame
22-36 hours
Title
Significant extracranial bleeding
Description
Extracranial bleeding, groin haematoma requiring evacuation / surgery or transfusion
Time Frame
Up to day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith W Muir, MD, FRCP
Organizational Affiliation
University of Glasgow
Official's Role
Principal Investigator
Facility Information:
Facility Name
NHS Greater Glasgow and Clyde
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
31564243
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.
Results Reference
derived
PubMed Identifier
27756804
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.
Results Reference
derived
PubMed Identifier
24298176
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.
Results Reference
derived
Learn more about this trial
Pragmatic Ischaemic Stroke Thrombectomy Evaluation
We'll reach out to this number within 24 hrs