Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours | NEJM

NEJM Group

18 Jul 202402:21

Summary

TLDRA phase 3 trial in China evaluated tenecteplase as a thrombolytic agent for ischemic stroke patients without access to thrombectomy. Administered 4.5 to 24 hours post-stroke, it showed a higher rate of patients with no disability at 90 days (33.0% vs. 24.2% with standard care). However, it also increased the risk of symptomatic intracranial hemorrhage (3.0% vs. 0.8%). The study suggests tenecteplase may offer benefits beyond the 4.5-hour window for eligible patients.

Takeaways

🏥 Large-vessel ischemic stroke patients without access to endovascular thrombectomy can benefit from tenecteplase administered within 4.5 hours.
🕒 Over two-thirds of ischemic stroke patients present beyond the 4.5-hour window or have an unknown onset time, limiting their treatment options.
🧪 A new trial explores the efficacy of tenecteplase administered 4.5 to 24 hours after stroke onset in eligible patients.
🏥 This phase 3 trial included 516 Chinese adults with ischemic stroke due to anterior-circulation large-vessel occlusion.
💉 Participants were randomized to receive intravenous tenecteplase at a dose of 0.25 mg per kg of body weight or standard medical treatment.
📊 The primary outcome measured was a modified Rankin scale score of 0 or 1 at day 90, indicating less disability.
🌟 Tenecteplase treatment showed a higher percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days (33.0%) compared to standard medical treatment (24.2%).
⚠️ A key safety concern was the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment, which was higher in the tenecteplase group (3.0%) than in the standard treatment group (0.8%).
👨‍⚕️ The authors conclude that tenecteplase administered 4.5 to 24 hours after stroke onset is more effective in reducing disability at 90 days in Chinese patients without thrombectomy access.
🔍 Full trial results can be found at NEJM.org for further detailed analysis and information.

Q & A

What is the significance of the treatment discussed in the script for patients with large-vessel ischemic stroke?
-The treatment discussed in the script is significant because it offers an effective thrombolytic agent, tenecteplase, for patients who do not have access to endovascular thrombectomy and present beyond the typical 4.5-hour window post-stroke onset.
What is the time frame for administering tenecteplase according to the new trial mentioned in the script?
-The new trial evaluated the efficacy and safety of tenecteplase when administered between 4.5 to 24 hours after stroke onset.
Which group of patients was included in the phase 3 trial?
-The phase 3 trial included 516 Chinese adults with ischemic stroke due to anterior-circulation large-vessel occlusion who had salvageable tissue 4.5 to 24 hours after stroke onset and did not have access to thrombectomy.
What was the dosage of tenecteplase administered in the trial?
-Patients were assigned to receive intravenous tenecteplase at a dose of 0.25 mg per kg of body weight, up to a maximum of 25 mg.
What was the primary outcome measure used in the trial?
-The primary outcome was a modified Rankin scale score at day 90, with higher scores indicating greater disability, and the goal was to achieve a score of 0 or 1.
What was the percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days in the tenecteplase group?
-In the tenecteplase group, 33.0% of patients had a modified Rankin Scale score of 0 or 1 at 90 days.
How did the tenecteplase treatment compare to standard medical treatment in terms of the primary outcome?
-The results favored tenecteplase treatment, which had a higher percentage of patients with no or minimal disability at 90 days compared to standard medical treatment.
What was the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment in the tenecteplase group?
-The incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was higher in the tenecteplase group, at 3.0%, compared to 0.8% in the standard medical treatment group.
What conclusion did the authors draw from the trial results?
-The authors concluded that in Chinese patients with ischemic stroke who did not have access to thrombectomy, tenecteplase administered 4.5 to 24 hours after stroke onset resulted in a higher percentage of patients with no disability at 90 days than standard medical treatment.
Where can the full trial results be found?
-The full trial results are available at NEJM.org.

Outlines

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💉 Tenecteplase for Ischemic Stroke Beyond 4.5 Hours

This paragraph discusses a clinical trial evaluating the effectiveness of tenecteplase, a thrombolytic agent, for patients with large-vessel ischemic stroke who cannot access endovascular thrombectomy. The trial focuses on administering tenecteplase between 4.5 to 24 hours after stroke onset. The study included 516 Chinese adults with ischemic stroke due to anterior-circulation large-vessel occlusion, who had salvageable tissue within the specified time frame and lacked access to thrombectomy. Participants were randomly assigned to receive either intravenous tenecteplase at a dose of 0.25 mg per kg (up to a maximum of 25 mg) or standard medical treatment. The primary outcome measured was the modified Rankin scale score at 90 days, with higher scores indicating greater disability. The results showed that tenecteplase treatment led to a higher percentage of patients (33.0%) achieving a score of 0 or 1, indicating no or minimal disability, compared to 24.2% in the standard treatment group. However, the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was higher in the tenecteplase group (3.0%) than in the standard treatment group (0.8%). The conclusion drawn is that in Chinese patients with ischemic stroke who cannot access thrombectomy, tenecteplase administered 4.5 to 24 hours after stroke onset is associated with a higher percentage of patients having no disability at 90 days than standard medical treatment.

Mindmap

Keywords

💡Ischemic Stroke

Ischemic stroke is a type of stroke caused by the blockage of blood flow to the brain, resulting in a lack of oxygen and nutrients to brain cells. In the script, it is mentioned that the trial focuses on patients with ischemic stroke who do not have access to endovascular thrombectomy, highlighting the importance of alternative treatments for this condition.

💡Endovascular Thrombectomy

Endovascular thrombectomy is a medical procedure used to remove blood clots in the arteries of the brain, thereby restoring blood flow and preventing further damage in ischemic stroke patients. The script notes that many patients do not have access to this procedure, which underscores the need for effective alternative treatments.

💡Tenecteplase

Tenecteplase is a thrombolytic agent, a type of medication that helps dissolve blood clots. In the context of the script, tenecteplase is administered within 4.5 hours of stroke onset as an effective treatment for patients who cannot undergo thrombectomy, and its efficacy is further evaluated for use between 4.5 to 24 hours post-stroke.

💡Modified Rankin Scale

The Modified Rankin Scale is a standardized measure used to assess the degree of disability or dependence in daily activities after a stroke. The script mentions that the primary outcome of the trial was a score of 0 or 1 on this scale at day 90, indicating that patients treated with tenecteplase had a higher percentage of achieving minimal or no disability.

💡Phase 3 Trial

A Phase 3 trial is a type of clinical trial that involves a large number of participants and is conducted to confirm the effectiveness of a new treatment and monitor its side effects. The script describes a Phase 3 trial evaluating the efficacy and safety of tenecteplase in ischemic stroke patients, emphasizing the rigorous testing required for new medical treatments.

💡Anterior-Circulation Large-Vessel Occlusion

Anterior-circulation large-vessel occlusion refers to a blockage in the major arteries that supply blood to the front part of the brain. The script specifies that the trial included patients with this type of occlusion, indicating the specific stroke subtype targeted by the study.

💡Salvageable Tissue

Salvageable tissue in the context of stroke refers to brain tissue that is still viable and can potentially recover with timely treatment. The script mentions that patients included in the trial had salvageable tissue up to 24 hours after stroke onset, suggesting that there was still hope for recovery even beyond the traditional 4.5-hour window.

💡Intravenous Administration

Intravenous administration is a method of delivering medication directly into the bloodstream through a vein. In the script, tenecteplase is administered intravenously, which is a common method for delivering thrombolytic drugs in stroke treatment.

💡Symptomatic Intracranial Hemorrhage

Symptomatic intracranial hemorrhage is a type of bleeding within the brain that causes symptoms and can be a serious complication of stroke treatment. The script notes that this complication was more common in patients treated with tenecteplase, highlighting the importance of weighing the risks and benefits of treatment.

💡Standard Medical Treatment

Standard medical treatment refers to the conventional care provided to patients, which may include medication, monitoring, and supportive care. The script compares the outcomes of patients receiving tenecteplase to those receiving standard medical treatment, providing a benchmark for evaluating the effectiveness of the new treatment.

💡NEJM.org

NEJM.org is the website of the New England Journal of Medicine, a leading medical journal. The script mentions that full trial results are available on this site, indicating the importance of peer-reviewed publications in disseminating medical research findings.

Highlights

Tenecteplase is an effective thrombolytic agent for large-vessel ischemic stroke patients without access to endovascular thrombectomy.

More than two-thirds of ischemic stroke patients present beyond 4.5 hours or with an unknown time of onset.

A new trial evaluates tenecteplase administered 4.5 to 24 hours after stroke onset.

The trial is a phase 3, multicenter, randomized study.

516 Chinese adults with ischemic stroke due to anterior-circulation large-vessel occlusion were included.

Patients had salvageable tissue 4.5 to 24 hours after stroke onset and did not have access to thrombectomy.

Patients were assigned to receive intravenous tenecteplase at a dose of 0.25 mg per kg of body weight up to 25 mg.

The control group received standard medical treatment.

The primary outcome measured was a modified Rankin scale score of 0 or 1 at day 90.

Tenecteplase treatment had a higher percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days (33.0%).

Standard medical treatment had a lower percentage of patients with a modified Rankin Scale score of 0 or 1 at 90 days (24.2%).

Symptomatic intracranial hemorrhage within 36 hours after treatment was higher with tenecteplase (3.0%) than with standard medical treatment (0.8%).

Tenecteplase administered 4.5 to 24 hours after stroke onset resulted in a higher percentage of patients with no disability at 90 days.

The study concludes that tenecteplase is more effective than standard medical treatment for ischemic stroke patients without thrombectomy access.

Full trial results are available at NEJM.org.