Format

Send to

Choose Destination
JAMA. 2020 Feb 20. doi: 10.1001/jama.2020.1511. [Epub ahead of print]

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

Author information

1
Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
2
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
3
Department of Radiology, the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
4
Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia.
5
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
6
Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
7
Department of Neurology, Austin Hospital, Austin Health, Heidelberg, Victoria, Australia.
8
Department of Radiology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
9
Department of Radiology, Austin Hospital, Austin Health, Heidelberg, Victoria, Australia.
10
School of Medicine, Faculty of Health, Deakin University, Victoria, Australia.
11
Department of Neurology, Christchurch Hospital, Christchurch, New Zealand.
12
Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
13
Melbourne Medical School, Department of Medicine and Neurology, The University of Melbourne and Western Health, Sunshine Hospital, St Albans Victoria, Australia.
14
Department of Neurology, Gold Coast University Hospital, Southport, Queensland, Australia.
15
Department of Radiology, Gold Coast University Hospital, Southport, Queensland, Australia.
16
Eastern Health and Eastern Health Clinical School, Department of Neurosciences, Monash University, Clayton, Victoria, Australia.
17
Department of Radiology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
18
Department of Radiology, Christchurch Hospital, Christchurch, New Zealand.
19
Department of Medicine, Ballarat Base Hospital, Ballarat, Victoria, Australia.
20
Department of Neurology, Royal North Shore Hospital and Kolling Institute, University of Sydney, St Leonards, New South Wales, Australia.
21
Department of Neurology, Liverpool Hospital, Liverpool, New South Wales, Australia.
22
Department of Neurology, Lyell McEwin Hospital, Adelaide, South Australia, Australia.
23
School of Clinical Sciences, Department of Medicine, Monash University, Clayton, Victoria, Australia.
24
Department of Neurology, Gosford Hospital, Gosford, New South Wales, Australia.
25
Department of Neurology, University Hospital Geelong, Deakin University, Geelong, Victoria, Australia.
26
Department of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia.
27
Department of Medicine, Southwest Healthcare, Warrnambool, Victoria, Australia.
28
Department of Neurology, Alfred Hospital, Prahran, Victoria, Australia.
29
Department of Medicine, Northeast Health, Wangaratta, Victoria, Australia.
30
Department of Medicine, Albury Base Hospital, Albury, New South Wales, Australia.
31
Department of Medicine, Goulburn Valley Health, Shepparton, Victoria, Australia.
32
Department of Medicine, Latrobe Regional Health, Traralgon, Victoria, Australia.
33
Department of Medicine, Campbelltown Hospital, Campbelltown, New South Wales, Australia.
34
Department of Aged Care and Rehabilitation, Bankstown-Lidcombe Hospital, Bankstown, New South Wales, Australia.
35
Department of Neurology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
36
Department of Neurology, Royal Brisbane and Women's Hospital and the University of Queensland, Brisbane, Queensland, Australia.
37
Maridulu budyari gumal, The Sydney Partnership for Health Education Research & Enterprise (SPHERE), University of New South Wales, Sydney, Australia.
38
Victorian Stroke Telemedicine service, Ambulance Victoria, Melbourne, Victoria, Australia.

Abstract

Importance:

Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase.

Objective:

To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke.

Design, Setting, and Participants:

Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria.

Interventions:

Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy.

Main Outcomes and Measures:

The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death.

Results:

All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]).

Conclusions and Relevance:

Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned.

Trial Registration:

ClinicalTrials.gov Identifier: NCT03340493.

PMID:
32078683
DOI:
10.1001/jama.2020.1511

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center