Double-Blind, Placebo-Controlled Randomized Trial on Low Dose Azithromycin Prophilaxis in Primary Antibody Deficiencies

BACKGROUND: Lacking protective antibodies, patients with Primary Antibody Deficiencies (PAD) suffer from frequent respiratory infections leading chronic pulmonary damage. Macrolides prophylaxis has been proven effective in chronic respiratory diseases. OBJECTIVE: We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in PAD patients. METHODS: We designed a three-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250 mg once daily three-times a week for 2 years) would reduce respiratory exacerbations in PAD with chronic infection-related pulmonary diseases. The primary endpoint was the number of annual respiratory exacerbations. Secondary endpoints included time to first exacerbation, antibiotic additional courses, number of hospitalizations and safety. RESULTS: Eighty-nine patients received azithromycin (n=44) or placebo (n=45). The number of exacerbations was 3.6 per patient-year (95%CI 2.5-4.7) in the azithromycin arm, and 5.2 (95%CI 4.1-6.4) in the placebo arm (p=0.02). In the azithromycin group the HR for having an acute exacerbation was 0.5 (95%CI 0.3-0.9, p=0.03) and the HR for hospitalization was 0.5 (95%CI 0.2-1.1, p=0.04). The rate of additional antibiotic treatment per patient-year was 2.3 (95%CI 2.1-3.4) in the intervention and 3.6 (95%CI 2.9-4.3) in placebo groups (p=0.004). H. influenzae and S. pneumoniae were the prevalent isolates and they were non-susceptible to macrolides in 25% of patients of both arms. Azithromycin's safety profile was comparable with placebo. CONCLUSION: The study reached the main outcome centered in the reduction of exacerbation episodes per patient-year with a consequent reduction of additional courses of antibiotics, and of risk of hospitalization.