Tenecteplase on par with alteplase for acute ischaemic stroke

Among Chinese patients with acute ischaemic stroke, intravenous (IV) tenecteplase is noninferior to the standard-of-care alteplase in achieving an excellent functional outcome, with a similar safety profile, when given within 4.5 hours of symptom onset, according to the TRACE-2* trial presented at ISC 2023.

In the TRACE-2 trial, 62 percent of the patients treated with tenecteplase achieved an excellent functional outcome, which was defined as an mRS** score of 0–1 at 90 days, compared with 58 percent of those treated with alteplase (risk ratio [RR], 1.07, 95 percent confidence interval [CI], 0.98–1.16). [ISC 2023, abstract LB5]

“The lower limit of the 95 percent CI of the RR was larger than the noninferiority margin, indicating that tenecteplase was noninferior but not superior to alteplase,” said Dr Shuya Li from Beijing Tiantan Hospital in Beijing, China, who presented the study.

In terms of safety, the overall rates of adverse events (AEs) were comparable between the tenecteplase and alteplase groups (86 percent vs 87 percent), as were the rates of serious AEs (16 percent vs 15 percent).

These findings were consistent with the recent AcT*** trial, which demonstrated that IV tenecteplase was noninferior to alteplase in terms of excellent functional outcomes at 90 days, with similar safety outcomes, in an Asian population with acute ischaemic stroke. [Lancet 2022;16;161-169]

“The findings of TRACE-2 trial in combination with the AcT trial further strengthen the evidence for noninferiority of tenecteplase compared with alteplase in treating patients with acute ischaemic stroke,” the researchers noted.

In the past decades, although multiple clinical research have proved that alteplase was always the major player and showed significant effects on reperfusion therapy, there is still an increasing interest in replacing alteplase with tenecteplase as the preferred thrombolytic treatment for patients with acute ischaemic stroke, said Li. [Lancet 2023;doi:10.1016/S0140-6736(22)02600-9]

Hence, the present study aimed to further establish the noninferiority of tenecteplase to alteplase in this patient population, she noted.

The researchers conducted a multicentre, open-label, noninferiority trial involving 1,430 Chinese adults with ischaemic stroke (median age 66 years, 68.5 percent male) who were eligible for standard IV thrombolysis but ineligible for endovascular thrombectomy. Within 4.5 hours of symptom onset, the participants were randomly assigned to receive either a single, IV bolus tenecteplase (0.25 mg/kg, with a maximum dose of 25 mg; n=716) or IV alteplase (0.9 mg/kg, with a maximum dose of 90 mg; n=714), with 10 percent of the dose given as a bolus, followed by an hour-long infusion. The primary efficacy outcome of the study was the proportion of patients who achieved an excellent functional outcome.

When a noncontrast CT imaging or MRI was performed to detect haemorrhage within 36 hours after randomization, similar rates of symptomatic intracranial haemorrhage were observed between the tenecteplase and alteplase groups (2 percent for both groups; RR, 1.18).

However, 46 patients died within 90 days after symptom onset in the tenecteplase group, while only 35 deaths were reported in the alteplase group.

Although the tenecteplase group showed numerically higher rates of symptomatic intracranial haemorrhage and death than the alteplase group, these findings did not reach statistical significance, the researchers noted. [Lancet 2023;doi:10.1016/S0140-6736(22)02600-9]

Moreover, there were no significant differences in the proportion of patients with favourable functional outcome (defined as an mRS score of 0–2), neurological improvement on NIHSS⁺ score (defined as a decrease of ≤4 points), improvement in European health-related quality of life, and Barthel Index score of ≥95 points between the two groups.

“Overall, tenecteplase was noninferior to alteplase with respect to the primary efficacy outcome in patients with ischaemic stroke treated within 4.5 hours of symptom onset,” Li said. “Given the ease of administration for tenecteplase, it is worth evaluating the efficacy and safety of IV tenecteplase with an extended time window from 4.5 to 24 hours in future studies.”

These findings also suggest that IV tenecteplase 0.25 mg/kg may be used as an alternative thrombolytic agent to alteplase in treating patients with acute ischaemic stroke, she added.

*TRACE-2: Tenecteplase reperfusion therapy in acute ischemic cerebrovascular events-II

**mRS: modified Rankin Scale

***AcT: Alteplase compared to tenecteplase in patients with acute ischemic stroke

⁺NIHSS: National Institutes of Health Stroke Scale