A Randomized, Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability of Influenza Virus Vaccine, Trivalent, Types A and B, Live, Cold-Adapted (CAIV-T) in Children and Adolescents with Asthma 1953

Background: Asthma is the most common chronic illness in childhood affecting at least 7% of persons < 18 years of age. Vaccination with inactivated, intramuscular influenza vaccine is recommended for children and adolescents with asthma, however, only a minority are vaccinated. CAIV-T administered intranasally recently was shown to be 93% effective in reducing culture positive influenza illness in healthy children 15-71 months of age. An intranasal vaccine may increase compliance in asthmatic children and adolescents. Objective: To investigate the safety and tolerability of intranasal CAIV-T compared to placebo in children and adolescents with moderate to severe asthma. Study Population: 48 asthmatic subjects, aged 9 - 17 years, were enrolled from 10/97 - 11/9. Methods: Subjects were screened 7 days prior to vaccination by spirometry, including forced expiratory volume (FEV₁), forced vital capacity (FVC) and forced expiratory flow during the first half of FVC. Inclusion criteria included FEV₁ <80% of predicted normal value ≥ 8 hours after the last dose of albuterol MDI, and a ≥ 12% increase in FEV₁ within 30 minutes of albuterol inhalation. Subjects also must have received a fixed regimen of asthma medication without an asthma exacerbation for 4 weeks prior to and 1 week following screening. On Day 0 subjects were randomized equally to receive 0.5ml of CAIV-T (10⁷ TCID₅₀ each of A/Shenzhen/227/95(H1N1), A/Wuhan/359/95(H3N2) and B/Harbin/7/94-like) or placebo (egg allantoic fluid containing sucrose-phosphate glutamate). Spirometry was obtained once on Day 3-5 post-vaccination for comparison to Day 0 baseline measures. Following vaccination, subjects recorded daily temperatures, reactogenicity symptoms(cough, sore throat, runny nose, headache, chills, muscle aches, and tiredness), all adverse events, peak expiratory flow rates, clinical asthma scores, and nighttime awakening scores. Results: Following intranasal vaccination with CAIV-T or placebo, there were no serious adverse events, and only one subject had an asthma exacerbation requiring a change of medication. The study will be unblinded and complete results presented.