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Pragmatic Ischaemic Stroke Thrombectomy Evaluation

Not Applicable
Terminated
Conditions
Acute Ischaemic Stroke
Interventions
Drug: Intravenous rtPA
Device: Mechanical thrombectomy
Registration Number
NCT01745692
Lead Sponsor
NHS Greater Glasgow and Clyde
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
65
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intravenous rtPAIntravenous rtPAIV 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
Intravenous rtPA and Mechanical ThrombectomyMechanical thrombectomyIV 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
Intravenous rtPA and Mechanical ThrombectomyIntravenous rtPAIV 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
Primary Outcome Measures
NameTimeMethod
modified Rankin ScaleDay 90 +/-7

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
NameTimeMethod
MortalityDay 90 +/-7
NIH Stroke Scale (NIHSS)72 hours

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)

modified Rankin ScaleDay 90 +/-7

Change in distribution of mRS scores adjusted for baseline variables

Immediate recanalisation rateEnd of procedure

Immediate (i.e. end of procedure) recanalisation rates in subjects undergoing interventional procedures (core lab assessed).

Home TimeDay 90 +/-7

Days spent at home between stroke and day 90

Symptomatic intracranial haemorrhage22-26h

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)

Angiographic patency22-36 hours

Angiographic patency at 22-36 hours (Core lab assessed), using CTA or MRA

Intracranial haemorrhage22-36 hours

Any intracranial haemorrhage on 22-36h CT or MRI

Significant extracranial bleedingUp to day 90

Extracranial bleeding, groin haematoma requiring evacuation / surgery or transfusion

Trial Locations

Locations (1)

NHS Greater Glasgow and Clyde

🇬🇧

Glasgow, United Kingdom

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