Ethical considerations and rationale of the MAKI trial: A multicenter double-blind randomized placebo-controlled trial into the preventive effect of palivizumab on recurrent wheezing associated with respiratory syncytial virus infection in children with a gestational age of 33-35weeks

Background: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is the most frequent cause of bronchiolitis during infancy. Long-term airway morbidity with recurrent post bronchiolitis wheezing (PBW) episodes, which are probably associated with respiratory infections, occurs in 30 to 70% of infants that were hospitalised with RSV LRTI. Methods: We set up a multicenter, placebo-controlled double-blind randomized clinical trial in healthy preterm infants born between 33 and 35. weeks gestational age (WGA). The children received either one-monthly intramuscular palivizumab or placebo injection during the RSV season with a minimum of 2 injections. Results: The primary objective was to determine the preventive effect of RSV immunoprophylaxis (palivizumab) on the development of recurrent wheezing during the first year of life. The primary outcome measure was the number of wheezing days during the first year of life as obtained by daily logs. As a secondary outcome nasal swabs were taken for viral analysis in case of respiratory symptoms. We will also examine wheezing at age 1, 3 and 6. years both reported by the parents and the general practitioner and quality of life as secondary outcomes. This trial is possible because RSV immunoprophylaxis, although effective in this population, is not completely used in the Netherlands due to its high costs. Conclusion: The Institutional review board (IRB) concluded the study has high clinical relevance because the benefit of 50% chance of protection by palivizumab outweighs the risk of side adverse events due to intramuscular administration of placebo.