Tenecteplase still feasible up to 24 hours after a stroke

Intravenous thrombolysis with tenecteplase up to 24 hours after a stroke appears to re-establish blood flow in patients with large-vessel acute ischaemic stroke selected with advanced imaging, the phase IIa CHABLIS-T study has shown.

The strategy achieved the primary outcome of major reperfusion without symptomatic intracranial haemorrhage (ICH) 24 –48 hours after thrombolysis in 32.6 percent of patients treated with tenecteplase 0.25 mg/kg dose and in 23.3 percent of those receiving the 0.32 mg/kg dose, reported study author Dr Xin Cheng from the Huashan Hospital of Fudan University in Shanghai, China at ISC 2022. [Abstract LBS7]

A longer time window for thrombolysis

“The results are the first to be reported [for thrombolysis] with tenecteplase in the extended time window,” said Cheng. “This suggests that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after ‘last known well’ through perfusion-imaging selection.”

Tenecteplase is a genetically modified variant of alteplase, which is the standard of care for thrombolysis in stroke. A recent trial of alteplase demonstrated its benefit between 4.5 and 9 hours of stroke onset in patients who had an ischaemic stroke but with salvageable brain regions as detected by perfusion imaging. [N Engl J Med 2019;380:1795-1803]

More evidence is forthcoming for tenecteplase, which is administered as a single-bolus, rather than a 1-hour infusion. In fact, three trials with tenecteplase are currently ongoing, which Cheng said, “are needed before we can even change practice.”

Finally, a new option?

Tenecteplase is US FDA-approved for acute myocardial infarction. The single-bolus infusion, coupled with greater fibrin specificity and lesser chances of fibrinogen depletion, also makes tenecteplase a potential alternative to alteplase for stroke, pointed out Cheng.

The CHABLIS-T study was conducted at 13 centres in China and included 86 patients with acute ischaemic strokes caused by large-vessel occlusions in the anterior circulation or severe stenosis, who were identified through head and neck CT angiography and penumbral mismatch on CT perfusion imaging. Patients were randomly assigned to tenecteplase 0.25 mg/kg or 0.32 mg/kg 4.5–24 hours after they were last seen well. Mean age was similar in the two arms (68 and 67 years, respectively).

Recanalization at 4 to 6 hours occurred in 44 percent of both groups. Rates of symptomatic ICH and any ICH were higher with the 0.25-mg/kg dose  (11.6 percent vs 9.3 percent and 48.8 percent vs 30.2 percent, respectively).

As for neurologic outcomes, an excellent functional outcome (defined as a Modified Rankin Scale (mRS) score of 0–1 at 90 days) was achieved in 28 percent of the 0.25 mg/kg group and 49 percent of the 0.32 mg/kg group. A good functional outcome (mRS, 0–2) occurred in 46 percent of the 0.25 mg/kg group and 60 percent of the 0.32 mg/kg group.

In an analysis combining both the tenecteplase groups, the primary outcome was more likely to be achieved with thrombolysis alone vs thrombolysis plus endovascular therapy (EVT; 40.4 percent vs 8.8 percent), with a lower rate of symptomatic ICH (5.8 percent vs 17.7 percent). The reasons for these differences, according to Cheng, deserve to be investigated.

“Tenecteplase seems to be quite effective and safe in those who do not need endovascular therapy," Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had EVT.”

Time to switch, but which dose?

Dr Tudor Jovin from the Cooper University Hospital, Cherry Hill, New Jersey, US commented that clearly, the study suggests a benefit. "In fact, our hospital already switched to tenecteplase. But we don’t know the best dose yet.”

Additionally, what the stroke community hopes to establish is whether tenecteplase is better vs no treatment, or alteplase, for stroke.