Format

Send to

Choose Destination
Lancet Neurol. 2017 Oct;16(10):781-788. doi: 10.1016/S1474-4422(17)30253-3. Epub 2017 Aug 2.

Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial.

Author information

1
Department of Neurology, Centre for Neurovascular Diseases, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway. Electronic address: nicola.logallo@helse-bergen.no.
2
Department of Neurology, Centre for Neurovascular Diseases, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
3
Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway.
4
Department of Neurology, Oslo University Hospital, Ullevål, Norway.
5
Department of Neurology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
6
Department of Neurology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
7
Department of Neurology, Drammen Hospital, Vestre Viken Hospital Trust, Norway.
8
Department of Medicine, Vestre Viken Hospital Trust, Bærum Hospital, Norway.
9
Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Neurology and Neuroscience Research Group, Stavanger University Hospital, Stavanger, Norway.
10
Department of Neurology, Telemark Hospital, Skien, Norway.
11
Department of Neurology, Haugesund Hospital, Haugesund, Norway.
12
Department of Neurology, Førde Central Hospital, Norway.
13
Department of Neurology, Nordland Hospital, Bodø, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
14
Department of Neurology, Molde, Helse Møre og Romsdal, Norway.
15
Department of Neurology, St Olav University Hospital, Trondheim, Norway.
16
Department of Neurology, Oslo University Hospital, Oslo, Norway.
17
Department of Neurology, Centre for Neurovascular Diseases, Haukeland University Hospital, Bergen, Norway; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.

Abstract

BACKGROUND:

Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase. Previous phase 2 trials of tenecteplase in acute ischaemic stroke have shown promising results. We aimed to investigate the safety and efficacy of tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis.

METHODS:

This phase 3, randomised, open-label, blinded endpoint, superiority trial was done in 13 stroke units in Norway. We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms, or who were eligible for bridging therapy before thrombectomy. Patients were randomly assigned (1:1) to receive intravenous tenecteplase 0·4 mg/kg (to a maximum of 40 mg) or alteplase 0·9 mg/kg (to a maximum of 90 mg), via a block randomisation schedule stratified by centre of inclusion. Patients were not informed of treatment allocation; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not. The primary outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 3 months. The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data. This study is registered with ClinicalTrials.gov, number NCT01949948.

FINDINGS:

Between Sept 1, 2012, and Sept 30, 2016, 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered. 1100 patients were randomly assigned to the tenecteplase (n=549) or alteplase (n=551) groups. The median age of participants was 77 years (IQR 64-79) and the median National Institutes of Health Stroke Scale score at baseline was 4 points (IQR 2-8). A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 (18%) patients in the tenecteplase group and 91 (17%) patients in the alteplase group. The primary outcome was achieved by 354 (64%) patients in the tenecteplase group and 345 (63%) patients in the alteplase group (odds ratio 1·08, 95% CI 0·84-1·38; p=0·52). By 3 months, 29 (5%) patients had died in the tenecteplase group compared with 26 (5%) in the alteplase group. The frequency of serious adverse events was similar between groups (145 [26%] in the tenecteplase group vs 141 [26%] in the alteplase group; p=0·74).

INTERPRETATION:

Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenecteplase is non-inferior to alteplase.

FUNDING:

Research Council of Norway.

PMID:
28780236
DOI:
10.1016/S1474-4422(17)30253-3
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center