Sotalol tablet clinical studies: Difference between revisions
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== | ==Clinical Studies== | ||
Betapace (sotalol hydrochloride) has been studied in life-threatening and less severe arrhythmias. In patients with frequent premature ventricular complexes (VPC), Betapace (sotalol hydrochloride) was significantly superior to placebo in reducing VPCs, paired VPCs and non-sustained ventricular tachycardia (NSVT); the response was dose-related through 640 mg/day with 80-85% of patients having at least a 75% reduction of VPCs. Betapace (sotalol hydrochloride) was also superior, at the doses evaluated, to propranolol (40-80 mg TID) and similar to quinidine (200-400 mg QID) in reducing VPCs. In patients with lifethreatening arrhythmias [sustained ventricular tachycardia/fibrillation (VT/VF)], Betapace (sotalol hydrochloride) was studied acutely [by suppression of programmed electrical stimulation (PES) induced VT and by suppression of Holter monitor evidence of sustained VT] and, in acute responders, chronically. | |||
In a double-blind, randomized comparison of Betapace and procainamide given intravenously (total of 2 mg/kg Betapace vs. 19 mg/kg of procainamide over 90 minutes), Betapace suppressed PES induction in 30% of patients vs. 20% for procainamide (p=0.2). | |||
<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = BETAPACE (SOTALOL HYDROCHLORIDE) TABLET [BAYER HEALTHCARE PHARMACEUTICALS INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c4caf469-f684-4f6d-98e8-b6a2fff1de98 | publisher = | date = | accessdate = }}</ref> | In a randomized clinical trial [Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) Trial] comparing choice of antiarrhythmic therapy by PES suppression vs. Holter monitor selection (in each case followed by treadmill exercise testing) in patients with a history of sustained VT/VF who were also inducible by PES, the effectiveness acutely and chronically of Betapace (sotalol hydrochloride) was compared with 6 other drugs (procainamide, quinidine, mexiletine, propafenone, imipramine and pirmenol). Overall response, limited to first randomized drug, was 39% for sotalol and 30% for the pooled other drugs. Acute response rate for first drug randomized using suppression of PES induction was 36% for Betapace vs. a mean of 13% for the other drugs. Using the Holter monitoring endpoint (complete suppression of sustained VT, 90% suppression of NSVT, 80% suppression of VPC pairs, and at least 70% suppression of VPCs), Betapace yielded 41% response vs. 45% for the other drugs combined. Among responders placed on long-term therapy identified acutely as effective (by either PES or Holter), Betapace, when compared to the pool of other drugs, had the lowest two-year mortality (13% vs. 22%), the lowest two-year VT recurrence rate (30% vs. 60%), and the lowest withdrawal rate (38% vs. about 75-80%). The most commonly used doses of Betapace (sotalol hydrochloride) in this trial were 320-480 mg/day (66% of patients), with 16% receiving 240 mg/day or less and 18% receiving 640 mg or more. | ||
It cannot be determined, however, in the absence of a controlled comparison of Betapace vs. no pharmacologic treatment (e.g., in patients with implanted defibrillators) whether Betapace response causes improved survival or identifies a population with a good prognosis. | |||
In a large double-blind, placebo controlled secondary prevention (postinfarction) trial (n=1,456), Betapace (sotalol hydrochloride) was given as a non-titrated initial dose of 320 mg once daily. Betapace did not produce a significant increase in survival (7.3% mortality on Betapace vs. 8.9% on placebo, p=0.3), but overall did not suggest an adverse effect on survival. There was, however, a suggestion of an early (i.e., first 10 days) excess mortality (3% on sotalol vs. 2% on placebo). In a second small trial (n=17 randomized to sotalol) where sotalol was administered at high doses (e.g., 320 mg twice daily) to high-risk post-infarction patients (ejection fraction <40% and either >10 VPC/hr or VT on Holter), there were 4 fatalities and 3 serious hemodynamic/electrical adverse events within two weeks of initiating sotalol.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = BETAPACE (SOTALOL HYDROCHLORIDE) TABLET [BAYER HEALTHCARE PHARMACEUTICALS INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c4caf469-f684-4f6d-98e8-b6a2fff1de98 | publisher = | date = | accessdate = }}</ref> | |||
==References== | ==References== | ||
Revision as of 06:03, 10 February 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Clinical Studies
Betapace (sotalol hydrochloride) has been studied in life-threatening and less severe arrhythmias. In patients with frequent premature ventricular complexes (VPC), Betapace (sotalol hydrochloride) was significantly superior to placebo in reducing VPCs, paired VPCs and non-sustained ventricular tachycardia (NSVT); the response was dose-related through 640 mg/day with 80-85% of patients having at least a 75% reduction of VPCs. Betapace (sotalol hydrochloride) was also superior, at the doses evaluated, to propranolol (40-80 mg TID) and similar to quinidine (200-400 mg QID) in reducing VPCs. In patients with lifethreatening arrhythmias [sustained ventricular tachycardia/fibrillation (VT/VF)], Betapace (sotalol hydrochloride) was studied acutely [by suppression of programmed electrical stimulation (PES) induced VT and by suppression of Holter monitor evidence of sustained VT] and, in acute responders, chronically.
In a double-blind, randomized comparison of Betapace and procainamide given intravenously (total of 2 mg/kg Betapace vs. 19 mg/kg of procainamide over 90 minutes), Betapace suppressed PES induction in 30% of patients vs. 20% for procainamide (p=0.2).
In a randomized clinical trial [Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) Trial] comparing choice of antiarrhythmic therapy by PES suppression vs. Holter monitor selection (in each case followed by treadmill exercise testing) in patients with a history of sustained VT/VF who were also inducible by PES, the effectiveness acutely and chronically of Betapace (sotalol hydrochloride) was compared with 6 other drugs (procainamide, quinidine, mexiletine, propafenone, imipramine and pirmenol). Overall response, limited to first randomized drug, was 39% for sotalol and 30% for the pooled other drugs. Acute response rate for first drug randomized using suppression of PES induction was 36% for Betapace vs. a mean of 13% for the other drugs. Using the Holter monitoring endpoint (complete suppression of sustained VT, 90% suppression of NSVT, 80% suppression of VPC pairs, and at least 70% suppression of VPCs), Betapace yielded 41% response vs. 45% for the other drugs combined. Among responders placed on long-term therapy identified acutely as effective (by either PES or Holter), Betapace, when compared to the pool of other drugs, had the lowest two-year mortality (13% vs. 22%), the lowest two-year VT recurrence rate (30% vs. 60%), and the lowest withdrawal rate (38% vs. about 75-80%). The most commonly used doses of Betapace (sotalol hydrochloride) in this trial were 320-480 mg/day (66% of patients), with 16% receiving 240 mg/day or less and 18% receiving 640 mg or more.
It cannot be determined, however, in the absence of a controlled comparison of Betapace vs. no pharmacologic treatment (e.g., in patients with implanted defibrillators) whether Betapace response causes improved survival or identifies a population with a good prognosis.
In a large double-blind, placebo controlled secondary prevention (postinfarction) trial (n=1,456), Betapace (sotalol hydrochloride) was given as a non-titrated initial dose of 320 mg once daily. Betapace did not produce a significant increase in survival (7.3% mortality on Betapace vs. 8.9% on placebo, p=0.3), but overall did not suggest an adverse effect on survival. There was, however, a suggestion of an early (i.e., first 10 days) excess mortality (3% on sotalol vs. 2% on placebo). In a second small trial (n=17 randomized to sotalol) where sotalol was administered at high doses (e.g., 320 mg twice daily) to high-risk post-infarction patients (ejection fraction <40% and either >10 VPC/hr or VT on Holter), there were 4 fatalities and 3 serious hemodynamic/electrical adverse events within two weeks of initiating sotalol.[1]
References
Adapted from the FDA Package Insert.