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| | #REDIRECT [[Tenecteplase#Clinical Studies]] |
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| __NOTOC__
| | [[Category: Cardiovascular Drugs]] |
| {{Tenecteplase}}
| | [[Category: Drug]] |
| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Studies==
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| ASSENT-2 was an international, randomized, double-blind trial that compared 30-day mortality rates in 16,949 patients assigned to receive an IV bolus dose of TNKase or an accelerated infusion of Activase® (Alteplase).1 Eligibility criteria included onset of chest pain within 6 hours of randomization and ST-segment elevation or left bundle branch block on electrocardiogram (ECG). Patients were to be excluded from the trial if they received [[GP IIb/IIIainhibitors]] within the previous 12 hours. TNKase was dosed using actual or estimated weight in a weight-tiered fashion as described in DOSAGE AND ADMINISTRATION. All patients were to receive 150–325 mg of [[aspirin]] administered as soon as possible, followed by 150–325 mg daily. Intravenous [[heparin]] was to be administered as soon as possible: for patients weighing ≤67 kg, heparin was administered as a 4000 unit IV bolus followed by infusion at 800 U/hr; for patients weighing >67 kg, [[heparin]] was administered as a 5000 unit IV bolus followed by infusion at 1000 U/hr. [[heparin]] was continued for 48 to 72 hours with infusion adjusted to maintain aPTT at 50–75 seconds. The use of [[GP IIb/IIIa inhibitors]] was discouraged for the first 24 hours following randomization. The results of the primary endpoint (30-day mortality rates with non-parametric adjustment for the covariates of age, Killip class, heart rate, systolic blood pressure and infarct location) along with selected other 30-day endpoints are shown in Table 1.
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| Rates of mortality and the combined endpoint of death or stroke among pre-specified subgroups, including age, gender, time to treatment, infarct location, and history of previous[[myocardial infarction]], demonstrate consistent relative risks across these subgroups. There was insufficient enrollment of non-Caucasian patients to draw any conclusions regarding relative efficacy in racial subsets.
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| Rates of in-hospital procedures, including [[percutaneous transluminal coronary angioplasty]] ([[PTCA]]), stent placement, [[intra-aortic balloon pump]]([[IABP]]) use, and [[coronary artery bypass graft]] ([[CABG]]) surgery, were similar between the TNKase and Activase®(Alteplase) groups.
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| TIMI 10B was an open-label, controlled, randomized, dose-ranging, angiography study which utilized a blinded core laboratory for review of coronary arteriograms.2Patients (n = 837) presenting within 12 hours of symptom onset were treated with fixed doses of 30, 40, or 50 mg of TNKase or the accelerated infusion of Activase and underwent coronary arteriography at 90 minutes. The results showed that the 40 mg and 50 mg doses were similar to accelerated infusion of Activase in restoring patency. TIMI Grade 3 flow and TIMI Grade 2/3 flow at 90 minutes are shown in Table 2. The exact relationship between coronary artery patency and clinical activity has not been established.
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| The angiographic results from TIMI 10B and the safety data from ASSENT-1, an additional uncontrolled safety study of 3,235 TNKase-treated patients, provided the framework to develop a weight-tiered TNKase dose regimen.3 Exploratory analyses suggested that a weight-adjusted dose of 0.5 mg/kg to 0.6 mg/kg of TNKase resulted in a better patency to bleeding relationship than fixed doses of TNKase across a broad range of patient weights.
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| The Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT 4 PCI) was a Phase IIIb/IV study designed to assess the safety and effectiveness of a strategy of administering full dose TNKase with a single bolus of 4000 U of [[unfractionated heparin]] in patients with ST segment elevation [[AMI]], in whom primary [[percutaneous coronary intervention]] ([[PCI]]) was planned, but in whom a delay of 1–3 hours was anticipated before [[PCI]]. The trial was prematurely terminated with 1667 randomized patients (75 of whom were treated in the United States) due to a numerically higher mortality in the patients receiving TNKase prior to primary [[PCI]] versus [[PCI]] without TNKase (median time from randomization to balloon of 115 minutes). The incidence of the 90‑day primary endpoint, a composite of death or cardiogenic shock or congestive heart failure (CHF) within 90 days, was 18.6% in patients treated with TNKase plus [[PCI]] versus 13.4% in those treated with [[PCI]] alone (p=0.0055; OR 1.39 (95% C.I. 1.11–1.74)).
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| There were trends toward worse outcomes in the individual components of the primary endpoint between TNKase plus [[PCI]] versus [[PCI]] alone (mortality 6.7% vs. 5.0%, respectively; cardiogenic shock 6.1% vs. 4.8%, respectively; and CHF 12.1% vs. 9.4%, respectively). In addition, there were trends towards worse outcomes in recurrent MI (6.1% vs. 3.5%, respectively; p=0.03) and repeat target vessel revascularization (6.6% vs. 3.6%, respectively; p=0.005) in patients receiving TNKase plus [[PCI]] versus [[PCI]] alone.
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| There was no difference in in‑hospital major bleeding between the two groups (5.6% vs. 4.4% for TNKase plus [[PCI]] vs. [[PCI]] alone, respectively). For patients treated with TNKase plus [[PCI]], in‑hospital rates of intracranial hemorrhage and total stroke were similar to those observed in previous trials (0.97% and 1.8%, respectively); however, none of the patients treated with [[PCI]] alone experienced a stroke (ischemic, hemorrhagic or other).
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| <ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = TNKASE (TENECTEPLASE) KIT [GENENTECH, INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=69e391bf-1250-4083-aa60-6aa41c33657f | publisher = | date = | accessdate = 6 February 2014 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| [[Category:Thrombolytic drugs]]
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| [[Category:Cardiovascular Drugs]] | |
| [[Category:Drugs]] | |
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