Pragmatic Ischaemic Stroke Thrombectomy Evaluation

NCT01745692 | Terminated DMC

• 2 other identifiers: GN11NE257TSA 2011/06
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Ischaemic Stroke

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• modified Rankin Scale

  Day 90+/-7

• Mortality

  Day 90 +/-7

• modified Rankin Scale

  Day 90 +/-7

• NIH Stroke Scale (NIHSS)

  72 hours

• Angiographic patency

  22-36 hours

Study Arms (2)

Intravenous rtPA

ACTIVE COMPARATOR

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

Intravenous rtPA and Mechanical Thrombectomy

EXPERIMENTAL

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

Device: Mechanical thrombectomy; Drug: Intravenous rtPA

Interventions

Mechanical thrombectomy DEVICE

Intravenous rtPA and Mechanical Thrombectomy

Intravenous rtPA DRUG

All patients receive IV alteplase

Also known as: alteplase

Intravenous rtPA; Intravenous rtPA and Mechanical Thrombectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator
• University of Edinburgh: collaborator
• Newcastle University: collaborator

Study Sites (1)

NHS Greater Glasgow and Clyde

Glasgow, G51 4TF, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 31564243 DERIVED

• 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.

  PMID: 27756804 DERIVED

• 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.

  PMID: 24298176 DERIVED

MeSH Terms

Interventions

Tissue Plasminogen Activator

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Keith W Muir, MD, FRCP

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2012
• First Posted: December 10, 2012
• Study Start: December 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: July 1, 2015
• Last Updated: October 26, 2015

Record last verified: 2015-10

Locations

GB (1)