TNKase was comparable to alteplase in reducing stroke-related disability¹

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This video will provide a brief overview of the Alteplase compared to Tenecteplase study, also known as the AcT study, which led to FDA approval of TNKase for the treatment of acute ischemic stroke in adult patients. Before we get started, let’s quickly review the Important Safety Information for TNKase.

Indication

Acute Ischemic Stroke

TNKase (tenecteplase) is indicated for the treatment of acute ischemic stroke (AIS) in adults.

Important Safety Information

Contraindications

TNKase is contraindicated in any patients with active internal bleeding, intracranial or intraspinal surgery or trauma within 2 months, known bleeding diathesis, current severe uncontrolled hypertension, and presence of intracranial conditions that may increase the risk of bleeding (for example, intracranial neoplasm, arteriovenous malformation, or aneurysm). TNKase is also contraindicated in patients for the treatment of AIS with active intracranial hemorrhage.

There is additional Important Safety Information later in the video.

Before getting into the data for TNKase, let’s take a look at this quote from a review article.

“The introduction of [TNKase] has had a significant impact on stroke thrombolysis. Importantly, the use of [TNKase] has not been associated with increased risk of intracranial hemorrhage.”

Now let’s take a look at the specifics of the AcT study.

AcT was a large, randomized, controlled clinical trial designed to investigate the non-inferiority of TNKase to alteplase in the treatment of acute ischemic stroke.

Patients experiencing a stroke were eligible for the study if they had a disabling neurological deficit. Although the trial enrolled patients who were treated within 0 to 4.5 hours of stroke symptom onset, the subset of patients treated within 0 to 3 hours was used to assess efficacy of TNKase because the comparator, alteplase, is approved for use within 0 to 3 hours of stroke symptom onset.

The intent-to-treat population consisted of 1147 patients who were treated within 3 hours of symptom onset.

Patients were randomized to receive TNKase or alteplase. Due to the differences in administration, this was an open‑label study with blinded outcome assessment.

TNKase was administered as a single 5‑second IV bolus, whereas alteplase was given as an IV bolus plus a 1-hour infusion. TNKase was given at the body-weight–tiered recommended dosage. The maximum dose of TNKase for stroke treatment is 25 milligrams.

Efficacy of TNKase was assessed as the proportion of patients treated within 3 hours of symptom onset achieving a modified Rankin Scale score of 0 to 1 at 90 to 120 days.

The intent-to-treat population included a broad population that was consistent across both treatment arms.

The mean age was 72 years. 53% of patients were male, and 47% were female.

The median baseline NIHSS score was 10.

The presence of a large vessel occlusion was detected in approximately 27% on baseline CT angiography, and the median time from stroke onset to thrombolysis was 108 minutes.

Results from AcT showed no significant difference between treatment groups, with 36.6% of patients treated with TNKase and 35.9% of patients treated with alteplase having achieved excellent functional outcomes, defined as a modified Rankin Scale score of 0 to 1, 90 to 120 days following a stroke.

Similar efficacy was observed across exploratory subgroups defined by age, gender, and baseline NIHSS score.

Safety data were comparable across treatment arms.

Similar rates of death, symptomatic intracranial hemorrhage, extracranial bleeding requiring blood transfusion, and orolingual angioedema were observed across both treatment arms.

Approximately 3% of patients experienced symptomatic intracerebral hemorrhaging within 24 hours of treatment with either TNKase or alteplase. How does that compare with your experience treating with thrombolytic agents?

In summary, TNKase is administered as a single 5‑second IV bolus.

Data from the AcT trial demonstrated no significant differences between treatment groups treated within 3 hours of symptom onset in achieving excellent functional outcomes 90 to 120 days post stroke.

Similarly, the safety profile of TNKase was demonstrated to be comparable to alteplase, with ~3% of patients experiencing 24-hour symptomatic intracerebral hemorrhage in both treatment arms.

Thanks for watching. If you’re interested in learning about the body-weight–tiered dosing and administration of TNKase for acute ischemic stroke in adults, you can find a downloadable Dosing Card and a full video demonstrating each step of the process at TNKase.com.

Indication

Acute Ischemic Stroke

TNKase (tenecteplase) is indicated for the treatment of acute ischemic stroke (AIS) in adults.

Important Safety Information

Contraindications

TNKase is contraindicated in any patients with active internal bleeding, intracranial or intraspinal surgery or trauma within 2 months, known bleeding diathesis, current severe uncontrolled hypertension, and presence of intracranial conditions that may increase the risk of bleeding (for example, intracranial neoplasm, arteriovenous malformation, or aneurysm). TNKase is also contraindicated in patients for the treatment of AIS with active intracranial hemorrhage.

Warnings and Precautions

Bleeding

TNKase can cause significant, sometimes fatal, internal or external bleeding, especially at arterial and venous puncture sites. Concomitant use of other drugs that impair hemostasis increases the risk of bleeding. Avoid intramuscular injections and trauma to the patient while on TNKase. Perform arterial and venous punctures carefully and only as required. To minimize bleeding from noncompressible sites, avoid internal jugular and subclavian venous punctures. If an arterial puncture is necessary during TNKase administration, use an upper extremity vessel that is accessible to manual compression, apply pressure for at least 30 minutes, and monitor the puncture site closely. Should serious bleeding that is not controlled by local pressure occur, discontinue any concomitant heparin or antiplatelet agents immediately and treat appropriately. 

The concomitant administration of heparin and aspirin with and following administration of TNKase for the treatment of acute ischemic stroke during the first 24 hours after symptom onset has not been investigated. Because heparin, aspirin, or TNKase may cause bleeding complications, carefully monitor for bleeding, especially at arterial puncture sites. Hemorrhage can occur 1 or more days after administration of TNKase, while patients are still receiving anticoagulant therapy.

In the following conditions, the risks of bleeding with TNKase therapy for all approved indications are increased and should be weighed against the anticipated benefits: recent major surgery or procedure, (for example, coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels); cerebrovascular disease; recent intracranial hemorrhage (if not contraindicated); recent gastrointestinal or genitourinary bleeding; recent trauma; hypertension: systolic BP above 175 mm Hg or diastolic BP above 110 mm Hg; acute pericarditis; subacute bacterial endocarditis; hemostatic defects including those secondary to severe hepatic or renal disease; significant hepatic dysfunction; pregnancy; diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions; septic thrombophlebitis or occluded AV cannula at seriously infected site; advanced age; patients currently receiving anticoagulants; or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.

Hypersensitivity

Hypersensitivity, including urticarial/anaphylactic reactions, have been reported after administration of TNKase (for example, anaphylaxis, angioedema, laryngeal edema, rash, and urticaria). Monitor patients treated with TNKase during and for several hours after administration. If symptoms of hypersensitivity occur, initiate appropriate therapy (for example, antihistamines, corticosteroids, or epinephrine).

Thromboembolism

The use of thrombolytics can increase the risk of thrombo-embolic events in patients with high likelihood of left heart thrombus, such as patients with mitral stenosis or atrial fibrillation.

Cholesterol Embolization

Cholesterol embolism has been reported in patients treated with thrombolytic agents. Investigate cause of any new embolic event and treat appropriately.  

Arrhythmias

Coronary thrombolysis may result in arrhythmias associated with reperfusion. It is recommended that anti-arrhythmic therapy for bradycardia and/or ventricular irritability be available when TNKase is administered.

Adverse Reactions

The most common adverse reaction is bleeding.

Drug Interactions

Drug/Laboratory Test Interactions

During TNKase therapy, results of coagulation tests and/or measures of fibrinolytic activity may be unreliable unless specific precautions are taken to prevent in vitro artifacts. Tenecteplase is an enzyme that, when present in blood in pharmacologic concentrations, remains active under in vitro conditions. This can lead to degradation of fibrinogen in blood samples removed for analysis.

Patient Counseling Information

Bleeding

Inform patients that bleeding can occur 1 or more days after administration of TNKase. Instruct patients to contact a healthcare provider if they experience signs or symptoms consistent with bleeding (for example, unusual bruising; pink or brown urine; red, black, or tarry stools; coughing up blood; vomiting blood or blood that looks like coffee grounds) or symptoms of a stroke.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety Information.