CONTEXT: Antimicrobial cardiac safety is of particular concern during the treatment of community-acquired pneumonia (CAP) in elderly patients, due to the presence of comorbid conditions and the use of multiple medications that may individually or synergistically affect cardiac repolarization. STUDY OBJECTIVE: To assess the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with CAP. DESIGN AND SETTING: Prospective, randomized, double-blind trial conducted at 47 hospitals in the United States. PATIENTS: Subjects > or = 65 years old with clinical signs/symptoms of CAP requiring initial parenteral therapy, including those with comorbidities. The safety population included 394 patients: 51.3% male; 85.3% white; mean age, 77.8 years. Two-thirds of the patients were > 75 years old, and 74.1% had a history of cardiac disease. INTERVENTIONS: Patients received IV/oral moxifloxacin (400 mg qd) or IV/oral levofloxacin (500 mg qd) for 7 to 14 days. Safety evaluations included 72 h of digital continuous 12-lead Holter monitoring, 12-lead ECGs at baseline and at maximum serum concentration on day 3, and adverse events. MAIN OUTCOME MEASURES: The primary safety end point was a composite of ventricular arrhythmia events based on Holter monitoring. RESULTS: Holter monitor data were available for 387 patients (192 receivingmoxifloxacin and 195 receiving levofloxacin). Sixteen moxifloxacin-treated patients (8.3%) and 10 levofloxacin-treated patients (5.1%) had a primary composite cardiac event (p = 0.29); most events were nonsustained ventricular tachycardia (VT) [14 patients receiving moxifloxacin, 7.3%; and 10 patients receiving levofloxacin, 5.1%]. One moxifloxacin-treated patient had sustained monomorphic VT (> 30 s), and one levofloxacin-treated patient had torsade de pointes. Mean +/- SD QTc (Fridericia formula) change on day 3 was + 6.4 +/- 23.2 ms for moxifloxacin and - 2.5 +/- 22.9 ms for levofloxacin (p = 0.04). No deaths clearly related to study drugs occurred during the observation period. CONCLUSIONS:IV/oral moxifloxacin, although known to cause QTc interval prolongation, has a comparable cardiac rhythm safety profile to IV/oral levofloxacin in high-risk elderly patients with CAP.
RCT Entities:
CONTEXT: Antimicrobial cardiac safety is of particular concern during the treatment of community-acquired pneumonia (CAP) in elderly patients, due to the presence of comorbid conditions and the use of multiple medications that may individually or synergistically affect cardiac repolarization. STUDY OBJECTIVE: To assess the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with CAP. DESIGN AND SETTING: Prospective, randomized, double-blind trial conducted at 47 hospitals in the United States. PATIENTS: Subjects > or = 65 years old with clinical signs/symptoms of CAP requiring initial parenteral therapy, including those with comorbidities. The safety population included 394 patients: 51.3% male; 85.3% white; mean age, 77.8 years. Two-thirds of the patients were > 75 years old, and 74.1% had a history of cardiac disease. INTERVENTIONS:Patients received IV/oral moxifloxacin (400 mg qd) or IV/oral levofloxacin (500 mg qd) for 7 to 14 days. Safety evaluations included 72 h of digital continuous 12-lead Holter monitoring, 12-lead ECGs at baseline and at maximum serum concentration on day 3, and adverse events. MAIN OUTCOME MEASURES: The primary safety end point was a composite of ventricular arrhythmia events based on Holter monitoring. RESULTS: Holter monitor data were available for 387 patients (192 receiving moxifloxacin and 195 receiving levofloxacin). Sixteen moxifloxacin-treated patients (8.3%) and 10 levofloxacin-treated patients (5.1%) had a primary composite cardiac event (p = 0.29); most events were nonsustained ventricular tachycardia (VT) [14 patients receiving moxifloxacin, 7.3%; and 10 patients receiving levofloxacin, 5.1%]. One moxifloxacin-treated patient had sustained monomorphic VT (> 30 s), and one levofloxacin-treated patient had torsade de pointes. Mean +/- SD QTc (Fridericia formula) change on day 3 was + 6.4 +/- 23.2 ms for moxifloxacin and - 2.5 +/- 22.9 ms for levofloxacin (p = 0.04). No deaths clearly related to study drugs occurred during the observation period. CONCLUSIONS: IV/oral moxifloxacin, although known to cause QTc interval prolongation, has a comparable cardiac rhythm safety profile to IV/oral levofloxacin in high-risk elderly patients with CAP.
Authors: Zhiqiang Kevin Lu; Jing Yuan; Minghui Li; S Scott Sutton; Gowtham A Rao; Sony Jacob; Charles L Bennett Journal: Expert Opin Drug Saf Date: 2014-12-10 Impact factor: 4.250