Cinzia Milito1, Federica Pulvirenti1, Francesco Cinetto2, Vassilios Lougaris3, Annarosa Soresina4, Antonio Pecoraro5, Alessandra Vultaggio6, Maria Carrabba7, Giuseppe Lassandro8, Alessandro Plebani3, Giuseppe Spadaro5, Andrea Matucci6, Giovanna Fabio7, Rosa Maria Dellepiane9, Baldassarre Martire8, Carlo Agostini2, Damiano Abeni10, Stefano Tabolli10, Isabella Quinti11. 1. Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy. 2. Department of Medicine DIMED, University of Padova, Padova, Italy. 3. Department of Clinical and Experimental Sciences, University of Brescia, and ASST-Spedali Civili of Brescia, Brescia, Italy. 4. Department of Pediatrics, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy. 5. Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research, University of Naples Federico II, Naples, Italy. 6. Immunoallergology Unit, Department Medical-Geriatric, AOU Careggi, Florence, Italy. 7. Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 8. Department of Biomedicine and Evolutive Age, University of Bari, Bari, Italy. 9. Department of Pediatrics, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. 10. Health Services Research Unit IDI, IRCCS, Rome, Italy. 11. Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy. Electronic address: isabella.quinti@uniroma1.it.
Abstract
BACKGROUND: Lacking protective antibodies, patients with primary antibody deficiencies (PADs) experience frequent respiratory tract infections, leading to chronic pulmonary damage. Macrolide prophylaxis has proved effective in patients with chronic respiratory diseases. OBJECTIVE: We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in patients with PADs. METHODS: We designed a 3-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250 mg administered once daily 3 times a week for 2 years) would reduce respiratory exacerbations in patients with PADs and chronic infection-related pulmonary diseases. The primary end point was the number of annual respiratory exacerbations. Secondary end points included time to first exacerbation, additional antibiotic 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 (95% CI, 2.5-4.7) per patient-year in the azithromycin arm and 5.2 (95% CI, 4.1-6.4) per patient-year in the placebo arm (P = .02). In the azithromycin group the hazard risk for having an acute exacerbation was 0.5 (95% CI, 0.3-0.9; P = .03), and the hazard risk for hospitalization was 0.5 (95% CI, 0.2-1.1; P = .04). The rate of additional antibiotic treatment per patient-year was 2.3 (95% CI, 2.1-3.4) in the intervention group and 3.6 (95% CI, 2.9-4.3) in the placebo group (P = .004). Haemophilus influenzae and Streptococcus pneumoniae were the prevalent isolates, and they were not susceptible to macrolides in 25% of patients of both arms. Azithromycin's safety profile was comparable with that of placebo. CONCLUSION: The study reached the main outcome centered on the reduction of exacerbation episodes per patient-year, with a consequent reduction in additional courses of antibiotics and risk of hospitalization.
RCT Entities:
BACKGROUND: Lacking protective antibodies, patients with primary antibody deficiencies (PADs) experience frequent respiratory tract infections, leading to chronic pulmonary damage. Macrolide prophylaxis has proved effective in patients with chronic respiratory diseases. OBJECTIVE: We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in patients with PADs. METHODS: We designed a 3-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250 mg administered once daily 3 times a week for 2 years) would reduce respiratory exacerbations in patients with PADs and chronic infection-related pulmonary diseases. The primary end point was the number of annual respiratory exacerbations. Secondary end points included time to first exacerbation, additional antibiotic 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 (95% CI, 2.5-4.7) per patient-year in the azithromycin arm and 5.2 (95% CI, 4.1-6.4) per patient-year in the placebo arm (P = .02). In the azithromycin group the hazard risk for having an acute exacerbation was 0.5 (95% CI, 0.3-0.9; P = .03), and the hazard risk for hospitalization was 0.5 (95% CI, 0.2-1.1; P = .04). The rate of additional antibiotic treatment per patient-year was 2.3 (95% CI, 2.1-3.4) in the intervention group and 3.6 (95% CI, 2.9-4.3) in the placebo group (P = .004). Haemophilus influenzae and Streptococcus pneumoniae were the prevalent isolates, and they were not susceptible to macrolides in 25% of patients of both arms. Azithromycin's safety profile was comparable with that of placebo. CONCLUSION: The study reached the main outcome centered on the reduction of exacerbation episodes per patient-year, with a consequent reduction in additional courses of antibiotics and risk of hospitalization.
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Authors: Bas M Smits; Ilona Kleine Budde; Esther de Vries; Ineke J M Ten Berge; Robbert G M Bredius; Marcel van Deuren; Jaap T van Dissel; Pauline M Ellerbroek; Michiel van der Flier; P Martin van Hagen; Chris Nieuwhof; Bram Rutgers; Lieke E A M Sanders; Anna Simon; Taco W Kuijpers; Joris M van Montfrans Journal: J Clin Immunol Date: 2020-11-18 Impact factor: 8.317