Clinical efficacy and time to symptom resolution of 5-day telithromycin versus 10-day amoxicillin–clavulanate in the treatment of acute bacterial sinusitis

ABSTRACT

Objective: This study compared the clinical efficacy, time to symptom resolution, and tolerability of a 5-day regimen of telithromycin with a 10-day regimen of high-dose amoxicillin–clavulanate in acute bacterial sinusitis (ABS).

Research design and methods: In this multinational (41 centers in Canada, Germany, Greece, Portugal, and Turkey), open-label, noninferiority study, patients ≥18 years old (n = 298) with a clinical ( > 7 days' symptoms) and radiological (air/fluid level, total opacification, mucosal thickening ≥10 mm) diagnosis of ABS were randomized to receive telithromycin 800 mg once daily for 5 days or amoxicillin–clavulanate 875/125 mg twice daily for 10 days. Clinical efficacy and tolerability were assessed at the test-of-cure visit (days 17–21). Time to symptom resolution was based on patients' daily diary assessment of individual symptoms.

Results: The per-protocol clinical success rate (primary endpoint) with telithromycin (88.6 % (109/123)) was noninferior to that with amoxicillin–clavulanate (88.8 % (111/125)) (95 % confidence interval: –8.9 to 8.5). In the modified intention-to-treat (mITT) population, the median time for 50 % reduction of total symptom scores was significantly shorter for telithromycin (4 days) vs. amoxicillin–clavulanate (5 days; p = 0.044); median times for 75 % reduction of total symptom scores were: telithromycin, 7 days; amoxicillin–clavulanate, 8 days (p = 0.115). The median time for reduction of total symptom scores to the absent/very mild category (mITT population) was 6 days for telithromycin vs. 8 days for amoxicillin–clavulanate (p = 0.04). All treatment-emergent adverse events (TEAEs) were mostly gastrointestinal and occurred in 20.7 % (30/145) of telithromycin-treated patients vs. 31.8 % (47/148) of amoxicillin–clavulanate-treated patients (p = 0.034). One serious AE was reported in the telithromycin group, but it was considered not to be related to treatment.

Conclusions: This open-label, randomized study demonstrated that treatment of ABS with telithromycin resulted in comparable clinical efficacy, shorter times to symptom resolution, and fewer total TEAEs than treatment with amoxicillin–clavulanate.

Key words: :

• Antibacterial agents
• Haemophilus influenzae
• Ketolides
• β-Lactam resistance
• Sinusitis
• Streptococcus pneumoniae

Acknowledgments

Declaration of interest: This study was supported by sanofi-aventis. The trial registration number is NCT00174694 (Clinicaltrials.gov). Editorial support in the form of medical writing assistance was provided by Adelphi Communications, with funding provided by sanofi-aventis.

Dr Desrosiers declares the following relationships with sanofi-aventis: investigator in sponsored clinical studies; lecturer for continuing medical educational activities; member of advisory boards. He has also received travel grants from sanofi-aventis. Dr Mösges has received research grant funding from sanofi-aventis. Dr Klossek has acted as a consultant for sanofi-aventis.

The authors would like to thank the study investigators:

Canada: François Lavigne, Guiseppe D'Ignazio, Daniel Shu, Ben Lasko, Amarjit Cheema, Jeffrey Werger, Robert Hekkenberg, Calvin Powell and Mark Samaha; Germany: Ludger Klimek, Claudia Brunswig-Pitschner, Roman Gorstein, Thomas Harder, Joachim Hennig, Björn Hufert, Silvia Kegel, Alfred Nachtsheim, Norbert Pasch, Andreas Rübekeil, Elke Hippke and Uta Thieme; Greece: Ioannis Danilidis, Vasilis Danilidis, Panagiotis Goumas, George Velegrakis and Eleftherios Ferekidis; Portugal: António Paiva, Maia Gomes, Pais Clemente, João Marta Pimentel, Ezequiel Barros, Gabao Veiga, Carlos Carvalho and João Bacelar; Turkey: Kemal Deger; Ferhan Oz, Mehmet Ada, Bulent Karci, Semih Sutay; Fikret Ileri; Metin Onerci, Orhan Gedikli, Alp Demireller and Halit Uzun.