Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study.

Abstract

BACKGROUND:

Tenecteplase (TNK) possesses several pharmacological characteristics superior to conventional alteplase (rt-PA), with well-established safety and efficacy profile in Caucasians. There exists controversy over the optimal dose of intravenous rt-PA for East Asians with acute ischaemic stroke (AIS). Current study aimed to determine the safety dose range of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) for patients with AIS in China.

METHODS:

This multicentre, prospective, randomised, open-label, blinded end-point, phase II study compared three tiers of 0.1, 0.25, 0.32 mg/kg rhTNK-tPA (to a maximum of 40 mg) with standard 0.9 mg/kg rt-PA (to a maximum of 90 mg) in patients who were eligible for intravenous thrombolysis. The safety outcome were symptomatic intracranial haemorrhage (sICH) within 36 hours.

RESULTS:

Between May 2018 and February 2020, 240 patients were randomly assigned to four group, 4 of whom did not receive study treatment. The intention-to-treat analysis included 236 patients. There was no difference in the improvement on National Institutes of Health Stroke Scale at day 14 in the 3 tiers and control group (63.3%, 77.2%, 66.7% vs 62.7%). The number of sICH was 3 of 60 (5.0%) in the 0.1 mg/kg group, none in the 0.25 mg/kg group, 2 of 60 (3.3%) in the 0.32 mg/kg group and 1 (1.7%) of 59 in the rt-PA group. There were no significant between-group differences in severe adverse events.

CONCLUSIONS:

Similar to the Caucasians, rhTNK-tPA was well tolerated in Chinese patients with AIS at all doses administered within 3 hours of symptom onset. The dose-efficacy profile of rhTNK-tPA needs to be established with future investigations.

TRIAL REGISTRATION NUMBER:

NCT04676659.

• Authors: Shuya Li, Yuesong Pan, Ziran Wang, Zhigang Liang, Huisheng Chen, Dong Wang, Yi Sui, Xingquan Zhao, Yilong Wang, WanLiang Du, Huaguang Zheng, Yongjun Wang
• Journal: Stroke and vascular neurology (Stroke Vasc Neurol) Vol. 7 Issue 1 Pg. 47-53 (02 2022) ISSN: 2059-8696 [Electronic] England
• PMID: 34429364 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Fibrinolytic Agents
• Tissue Plasminogen Activator
• Tenecteplase

Topics

• Brain Ischemia (diagnosis, drug therapy)
• Fibrinolytic Agents
• Humans
• Ischemic Stroke (diagnosis, drug therapy)
• Prospective Studies
• Stroke (diagnosis, drug therapy)
• Tenecteplase (adverse effects)
• Tissue Plasminogen Activator (adverse effects)
• Treatment Outcome
• United States