A phase II double-blind randomised, placebo-controlled clinical trial of oral nitazoxanide for the treatment of bronchiolitis in infants presenting to hospital emergency departments.

Aims: Bronchiolitis is an extremely common cause of respiratory illness in infants caused by viral infection. The primary aim of this study is to determine whether treatment with nitazoxanide (NTZ) reduces the duration and severity of respiratory symptoms caused by bronchiolitis. Justification: Bronchiolitis affects over a third of infants in their first two years of life, and in Australia approximately 5,000 infants are hospitalised every year with the condition (Garcia et al. 2010). This is estimated to cost the healthcare system between 32 and 62 million dollars per year (Deshpande & Northern 2003). Infants who are born prematurely, or who have lung disease or heart disease are at the highest risk of developing bronchiolitis and also have the most severe disease. Bronchiolitis increases the risk of subsequently developing recurrent wheezing and asthma in childhood (Shay et al. 1999). An effective treatment would be of enormous benefit, not only by reducing infant suffering, but also by reducing the impact on parents and the healthcare system and the long-term consequences of infection. Participant Groups: This study will involve 124 infants between the ages of 1 and 12 months with a clinical diagnosis of bronchiolitis (62 in each study arm). Project Design: This study is a phase II double-blind randomised, placebo-controlled clinical trial of oral nitazoxanide for the treatment of bronchiolitis. Methods: Parents of infants presenting to Princess Margaret Hospital and diagnosed with bronchiolitis will be invited to participate. Following a full explanation of the study, informed consent will be taken from interested parents. A brief clinical history of the illness will be taken, and the infant assessed for respiratory distress using a validated scoring system (the Respiratory Distress Assessment Instrument). A painless swab will be taken from the front of the infant’s nose to try and detect the virus that has triggered the illness. Infants will then be allocated at random (similar to tossing a coin) to receive either treatment with NTZ or placebo for five days. Infants will be reviewed after three days of treatment, and their respiratory distress score repeated. The change in the score, combined with a change in respiratory rate will be used to calculate the Respiratory Assessment Change Score (RACS). In order to assess if NTZ is a useful treatment for bronchiolitis the RACS will be compared between the placebo and the NTZ groups. Symptoms over the first week of illness and oxygen requirement will also be compared using a parental completed diary card. To see if NTZ reduces the amount of virus present, a nasal swabs at day 3 and day 5 will be collected and the viral load compared with that at baseline. For infants that need to be admitted to hospital, the amount of medical support need ed will be recorded (for example, the need for oxygen therapy) as well as the duration of hospitalisation. The number of times that the infant has to come back to hospital for either bronchiolitis or wheeze will be recorded over the six months after treatment using electronic hospital records. Expected Outcomes: This study will determine whether NTZ is an effective empirical treatment for bronchiolitis. It will also help us to understand what effect NTZ has on the amount of virus present and how viral load changes over the course of the disease. If this study shows that NTZ is a useful treatment, then a larger study will be conducted enrolling infants that present to primary care facilities.