Tumor-disrupting drug may increase stroke treatment time

Alteplase dissolves blood clots that are blocking an artery that supplies oxygen-rich blood to the lungs or brain and has been approved by the FDA for the immediate treatment of ischemic stroke since 1996.

Tenecteplase, a new drug, is also a clot-dissolving drug and a biological variant of alteplase, and studies are underway to determine safety, efficacy, and parameters. its treatment for ischemic stroke.

Previous studies of Tenecteplase for the treatment of patients with acute ischemic stroke suggested that it may not be inferior to alteplase and may be better in the treatment of large-vessel stroke.

“The burden of stroke continues to increase worldwide, especially in China,” said Xin Cheng, MD, Ph.D., lead author of the study and associate professor of neurology at Huashan hospital. countries, where stroke is the leading cause of death. of Fudan University and the National Center for Neurological Disorders in Shanghai, China.

“There are two major limitations to thrombolysis [treatment to dissolve dangerous clots and restore blood flow] with alteplase: limited duration of 4.5 hours and low success rate in reopening arteries and restoring blood flow when a large cerebral vessel is blocked. “

To evaluate the potential of using tenecteplase to treat patients with large vessel strokes, Cheng and colleagues studied 86 ischemic stroke patients treated at 13 different hospitals in China. The patients had brain images taken between 4.5 and 24 hours after they were last known to be free of stroke symptoms.

On imaging, all study participants were found to have large, affected brain regions that could potentially be saved if blood flow were re-established and some small areas unlikely to benefit from treatment (known as bilateral mismatch).

Study participants were randomly divided into two groups:

  • 43 patients (mean age 68 years; 58.1% male) received a lower dose of tenecteplase (0.25 mg/kg); and
  • 43 patients (mean age 67 years; 72.1% men) received a higher dose of tenecteplase (0.32 mg/kg).
  • The researchers identified a positive, combined, pre-established safety and efficacy outcome if massively restored blood flow without symptoms of cerebral hemorrhage within 24-48 hours of treatment. treat.

    If more than 7 of 43 patients met the positive outcome criteria, the intervention dose of tenecteplase would be considered promising enough to warrant further study. In addition to tenecteplase, some patients undergo endovascular therapy (thrombectomy) to mechanically remove the clot, at the discretion of the treating physician.

    The researchers found:

  • At the lower tenecteplase dose, 14 of 43 patients (32.6%) achieved the indicated positive outcome endpoint.
  • At the higher tenecteplase dose, 10 of 43 patients (23.3%) achieved the indicated positive outcome endpoint.
  • Of all the study participants who were evaluated 3 months after treatment, more than half (53.5%) of the patients were not so severely disabled that they were unable to perform all prior activities but were not severely disabled. needed daily assistance, and 38.4% of the participants had no significant residual neurological impairment or mild symptoms but were able to return to activities of daily living before the stroke.
  • “Tenecteplase has been shown to be safe and powerful in re-establishing blood flow through blocked large brain vessels, thereby preventing potentially fatal brain tissue damage.

    Using perfusion images [to measure blood flow throughout the blood vessels] In order to evaluate patients with potentially larger areas of brain tissue that are potentially salvageable and smaller areas that have been lost to stroke, it seems possible that with tenecteplase we could extend the duration of treatment up 24 hours after the patient’s last visit. known as well.

    However, we still need more data from randomized controlled trials before changing practice to include regular tenecteplase,” Cheng said.

    In a small group of patients who received tenecteplase and underwent endovascular therapy (also called thrombectomy or mechanical clot removal), fewer patients (3 out of 34, or 8.8% ) achieved the primary outcome of restoring blood flow without symptoms of cerebral hemorrhage, compared with those who received tenecteplase only (21 out of 52, or 40.4%).

    “In our study, tenecteplase appeared to be quite effective and safe in patients who did not require endovascular therapy. More research is needed to understand why tenecteplase is less effective at restoring blood flow and more likely to lead to symptomatic brain bleeding in those who were Cheng said.

    As a Phase 2a trial, the focus of this study is to assess whether a treatment is safe and effective enough to advance to a larger clinical trial with more study participants. and to determine appropriate potential drug dosages for further studies.

    Based on the results of this trial, a lower dose of tenecteplase is being evaluated in a larger, nationwide, phase 2b study in China to compare the efficacy and safety of tenecteplase vs. standard.

    Study limitations include being a phase 2a clinical trial without a control group, and these results from China may not be generalizable to non-Chinese populations.

    “Stroke involving the large arteries in the brain due to plaque buildup is much more common in people of Chinese or Asian ancestry than in people of Caucasian ancestry.

    These types of strokes typically have more blood flow through the accessory vessels than embolic strokes, which are caused by blood clots that form elsewhere in the body and travel to the brain.

    The optimal strategy to restore blood flow in patients with large atherosclerotic plaque accumulation is unknown, and there is a question of whether endovascular therapy is advisable. [thrombectomy] is appropriate and effective in this type of stroke.

    Given the large stroke burden and limited access to endovascular capacity centers in China, a potent venous thrombolytic drug such as tenecteplase may make more sense,” Cheng said. .

    The latest ischemic stroke guidelines from the American Heart Association suggest it may be reasonable to consider tenecteplase for the treatment of ischemic stroke in selected patients. Several recent clinical trials focusing on ischemic stroke have directly compared alteplase and tenecteplase, however, large phase 3 trials are still ongoing.

    Source: Eurekalert

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