麻豆传媒

Tenecteplase (TNKase) appeared feasible for thrombolysis in acute ischemic stroke in patients presenting up to 24 hours after symptom onset, a phase II trial suggested.

The typical 0.25 mg/kg dose of the drug achieved at least 50% reduction in hypoperfusion lesion volume (or mTICI 2b flow for those treated with thrombectomy) without symptomatic intracranial hemorrhage at 24 to 48 hours after thrombolysis in 32.6% of patients.

A higher dose, 0.32 mg/kg, didn't do better on that measure (23.3%), reported Xin Cheng, MD, of Huashan Hospital and the National Center for Neurological Disorders in Shanghai, at the American Stoke Association International Stroke Conference (ISC), held virtually and in New Orleans.

The proportion of patients with good functional outcome at 90 days (modified Rankin Scale score 0-2) was 46.5% with the lower dose and 60.5% with the higher one.

Findings like this are important for centers like that of ISC program vice-chair Tudor G. Jovin, MD, of the Cooper Neurological Institute in Camden, New Jersey, where routine stroke thrombolysis has switched from alteplase (Activase) to tenecteplase.

"I think we are going to see more centers switching, so this is an important question," Jovin commented at an ISC press conference.

The signal of benefit is there compared with the natural history of untreated wake-up or late-presenting stroke, he said, achieving the aim of a phase II trial.

"But the study did not directly aim to answer whether [tenecteplase] in this setting is better than no treatment, which is the standard," or is better when added to endovascular therapy for those candidates, or whether it's better than alteplase in this setting, Jovin noted.

The lower 0.25 mg/kg dose -- the one typically used off-label for stroke in U.S. practice -- was chosen for the phase IIb follow-up study, dubbed CHABLIS-T II, but even more data will be needed from randomized controlled clinical trials before the findings can change clinical practice, Cheng cautioned.

ISC press conference moderator Mitchell Elkind, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York City, agreed.

"As in any study done in a single location, we want to see additional studies in other settings replicate those findings before we accept it completely," said Elkind, who is American Heart Association immediate past president. "But technically, it looks pretty similar to what we do here in terms of the drugs itself."

Other trials underway include the , , and trials, all comparing tenecteplase at 0.25 mg/kg against standard of care or placebo in patients presenting up to 24 hours after time last known well.

Whether tenecteplase's results are similar in patients treated with endovascular therapy and without it will also require study, Cheng pointed out at the late-breaking clinical trial session.

Trials have shown at least with tenecteplase as with alteplase in stroke thrombolysis, but been limited only to the conventional window of up to 6 hours after stroke onset. Cheng's group took the next step to look beyond that window.

Their Chinese Acute Tissue-Based Imaging Selection for Lysis In Stroke-Tenecteplase () study enrolled a total of 86 adults who had anterior large vessel occlusion or severe stenosis ischemic stroke with significant penumbral mismatch on perfusion CT at 4.5 to 24-hours from time last seen well. Enrollment was staged to stop the lower dose arm if too few patients had a good outcome after the first 18 were treated.

The trial used a Chinese recombinant human TNK tissue-type plasminogen activator approved there for cardiac but not stroke indications. Participants were randomized to the two dose groups.

Safety outcomes showed symptomatic intracerebral hemorrhage in 11.6% of patients treated with the 0.25 mg/kg dose and 9.3% treated with 0.32 mg/kg tenecteplase, while any intracerebral hemorrhage occurred in 48.8% and 30.2%, respectively. Parenchymal hematoma type 2 at 24 to 48 hours occurred in 5.8% of the lower dose and 11.8% of the higher dose group. Death or severe disability at 90 days occurred in 21.2% and 20.6%, respectively.

Study limitations included lack of a control group and small sample size, as well as the inclusion of only Chinese patients, for whom stroke characteristics may differ from patients elsewhere.

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