Acute otitis media (AOM) is one of the most common illnesses of childhood, with a peak incidence between 6 and 24 months of age. AOM is also the most common indication for antibiotic use among U.S. children, and as such, contributes significantly to the growing problem of antimicrobial resistance. A safe and effective means of preventing AOM without the use of antibiotics would be of great public health importance. Xylitol, a naturally occurring sugar alcohol, has been proposed as a prophylactic therapy for AOM. In two recent, well-designed, randomized, double-blind clinical trials conducted by a single research team in Finland, daily treatment with xylitol for two to three months was found to reduce the cumulative incidence of AOM in children by 30-40%, and to reduce antibiotic use by 36%. Older children consumed xylitol in the form of a chewing gum or lozenge, while children too young to chew gum received xylitol as syrup. However, most participants in the Finnish trials were beyond the age range of greatest risk for AOM, and all received xylitol five times per day. If xylitol is to be useful as a widespread prophylactic treatment for AOM, it must be shown that it can be given safely over several months to children between 6 and 24 months of age and that it is effective when given less frequently than five times per day. The applicants' ultimate goal is to conduct a large randomized controlled trial (RCT) to test whether xylitol, given one to three times a day as an aqueous solution to children between the ages of 6 and 24 months, significantly reduces the risk of AOM and antibiotic use. The current application proposes a two-phase pilot study to collect preliminary data necessary to ensure the success of a large RCT. Phase I consists of a seven-day dose-ranging tolerability study intended to determined the palatability and side effects (particularly gastrointestinal symptoms) of varying doses of xylitol solution given to children six to 24 months of age. Phase II consists of a six-month pilot RCT of xylitol solution versus control (sorbitol) solution administered once daily or three times a day to children six to 24 months old for six months. The pilot RCT will be conducted within the SIone Epidemiology Unit Network of Pediatricians and Family Practitioners, a nationwide physician research network. The pilot RCT will allow testing and refinement of subject enrollment procedures and data collection instruments. A preliminary estimate of the effect size of xylitol treatment from the pilot RCT will suggest whether the effect if sufficiently large to warrant a large formal RCT to be proposed. ? ?
| Vernacchio, Louis; Vezina, Richard M; Mitchell, Allen A (2007) Tolerability of oral xylitol solution in young children: implications for otitis media prophylaxis. Int J Pediatr Otorhinolaryngol 71:89-94 |
