Tenecteplase yields worse safety and functional outcomes compared to alteplase in ischaemic stroke: Lancet
In a dose of 0·4 mg/kg tenecteplase yielded worse safety and functional outcomes compared with alteplase in a prematurely terminated study. The study failed to establish non-inferiority of tenecteplase to alteplase in moderate and severe ischaemic stroke, according to a recent study published in The Lancer- Neurology. Tenecteplase is a modified tissue plasminogen...
In a dose of 0·4 mg/kg tenecteplase yielded worse safety and functional outcomes compared with alteplase in a prematurely terminated study. The study failed to establish non-inferiority of tenecteplase to alteplase in moderate and severe ischaemic stroke, according to a recent study published in The Lancer- Neurology.
Tenecteplase is a modified tissue plasminogen activator with pharmacological and practical advantages over alteplase—which is currently the only approved thrombolytic drug for ischaemic stroke. The NOR-TEST trial showed that 0·4 mg/kg of tenecteplase had an efficacy and safety profile similar to that of a standard dose (0·9 mg/kg) of alteplase, albeit in a patient population with a high prevalence of minor stroke. The aim of NOR-TEST 2 was to establish the non-inferiority of tenecteplase 0·4 mg/kg to alteplase 0·9 mg/kg for patients with moderate or severe ischaemic stroke. This phase 3, a randomised, open-label, blinded endpoint, the non-inferiority trial was performed at 11 hospitals with stroke units in Norway. Patients with suspected acute ischaemic stroke with a National Institutes of Health Stroke Scale score of 6 or more who were eligible for thrombolysis and admitted within 4·5 h of symptom onset were consecutively included. Random assignment, done by a computer with a block size of 4 and with allocations placed into opaque envelopes to be opened consecutively, was 1:1 between intravenous tenecteplase (0·4 mg/kg) or standard-dose alteplase (0·9 mg/kg). Doctors and nurses providing acute care were not masked to treatment, but primary outcome assessment at 3 months was masked. The primary outcome was a favourable functional outcome defined as a modified Rankin Scale score of 0–1 at 3 months, assessed in the modified intention-to-treat analysis (excluding patients who did not qualify for thrombolysis after randomisation or who withdrew informed consent). The non-inferiority margin was 3%. This trial (NOR-TEST 2) is registered with EudraCT (number 2018–003090–95) and ClinicalTrials.gov (NCT03854500). The trial was stopped early for safety reasons and is designated part A for analysis. Part B is ongoing with a lower dose of tenecteplase (0·25 mg/kg).
Findings of the study are:
- Between Oct 28, 2019, and Sept 26, 2021, 216 patients were enrolled.
- Patient enrolment was stopped after a per-protocol safety review showed an imbalance in the rates of symptomatic intracranial haemorrhage between the treatment groups, which surpassed the prespecified criteria for stopping the trial.
- Of 204 patients entering the modified intention-to-treat analysis, 100 were randomly allocated tenecteplase, and 104 were allocated alteplase.
- All patients were followed up within 14 days of the end of the 3-months follow-up period. A favourable functional outcome was reported less frequently in tenecteplase patients than in alteplase.
- Any intracranial haemorrhage was significantly more frequent with tenecteplase than with alteplase.
- Mortality at 3 months was also significantly higher with tenecteplase (15 [16%] of 96 patients) than with alteplase.
- Numerically more cases of symptomatic intracranial haemorrhage were reported with tenecteplase.
Thus, in this prematurely terminated study (terminated to fulfil the prespecified safety criteria), tenecteplase at a dose of 0·4 mg/kg yielded worse safety and functional outcomes than alteplase. Their study consequently could not show that 0·4 mg/kg tenecteplase is non-inferior to alteplase in moderate and severe ischaemic stroke. Future stroke trials should assess a lower dose of tenecteplase versus alteplase in moderate or severe stroke patients.
Tenecteplase versus alteplase for managing acute ischaemic stroke in Norway (NOR-TEST 2, part A): a phase 3, randomised, open-label, blinded endpoint, non-inferiority trial by Christopher Elnan Kvistad, et al. published in the Lancet Neurology.
Dr. Shravani Dali has completed her BDS from Pravara institute of medical sciences, loni. Following which she extensively worked in the healthcare sector for 2+ years. She has been actively involved in writing blogs in field of health and wellness. Currently she is pursuing her Masters of public health-health administration from Tata institute of social sciences. She can be contacted at firstname.lastname@example.org.