Rapid immunization against H5N1: a randomized trial evaluating homologous and cross-reactive immune responses to AS03(A)-adjuvanted vaccination in adults.

BACKGROUND: Accelerated immunization schedules may help gain early control of influenza pandemics. We investigated different schedules of an AS03(A)-adjuvanted H5N1 vaccine. METHODS: This phase II, open-label, 6-month study randomized participants (aged 18-64 years) to 2 vaccine doses administered 21 (standard schedule), 14, or 7 days apart, or on the same day. Coprimary end points were that the lower limit of the 98.75% confidence interval 14 days after the last dose must be (1) >40% for seroconversion rate (SCR) (Center for Biologics Evaluation and Research [CBER] criterion) and (2) >50% for seroprotection rate (SPR) (attainment rate for reciprocal hemagglutination inhibition titers ≥40, protocol-defined criterion) for the vaccine homologous strain (A/Indonesia/5/2005). European Committee for Human Medicinal Products (CHMP) immunogenicity criteria were also evaluated. RESULTS: Coprimary end points were achieved (lower 98.75% confidence intervals exceeded defined values). Titers were highest with the standard schedule. Nevertheless, CBER SCR, protocol-defined SPR, and CHMP criteria were met with all schedules for the A/Indonesia/5/2005 strain. There were no significant differences between age groups (18-40 vs 41-64 years). Immune response was robust against drift variants A/turkey/Turkey/1/2005 and A/Vietnam/1194/2004. CONCLUSIONS: The AS03(A)-adjuvanted H5N1 vaccine in accelerated schedules offers a robust immune response against vaccine homologous and drift variant strains, allowing consideration of compressed vaccination intervals. CLINICAL TRIALS REGISTRATION: NCT00695669.

Efficacy and tolerability of telithromycin for 5 or 10 days vs amoxicillin/clavulanic acid for 10 days in acute maxillary sinusitis.

Telithromycin (HMR 3647) is a new ketolide antimicrobial that was developed for the treatment of community-acquired respiratory tract injections. We conducted a randomized, double-blind, multicenter study to compare the clinical efficacy and safety of oral telithromycin, at 800 mg once daily for 5 or 10 days, with that of amoxicillin/clavulanic acid, at 500/125 mg three times daily for 10 days, in adults with acute maxillary sinusitis (AMS). A total of 754 patients with AMS of less than 28 days' duration were randomized to receive either telithromycin for 5 days followed by placebo for 5 days, telithromycin for 10 days, or amoxicillin/clavulanic acid for 10 days. Clinical outcome was assessed at a test-of-cure (TOC) visit between days 17 and 24 and at a late post-therapy visit between days 31 and 45. Analysis of clinical outcome on a per-protocol basis (n = 434) demonstrated therapeutic equivalence among the three regimens at the TOC visit; in each treatment group, the clinical cure rate was approximately 75%. Only a few patients (3 to 5 in each group) had relapsed by the late post-therapy follow-up visit. Telithromycin was generally safe and well tolerated. The most common adverse events were mild or moderate gastrointestinal effects, which occurred with similar frequency in all three groups. We conclude that 5 or 10 days of telithromycin at 800 mg once daily is as effective clinically and as well tolerated as 10 days of treatment with amoxicillin/clavulanic acid. Telithromycin, therefore, appears to be a valuable option for the treatment of AMS.