Long term effects of azithromycin in patients with cystic fibrosis: a double blind, placebo controlled trial
- 1AP-HP, Hôpital Trousseau, Pediatric Pulmonary Department, Paris; Inserm, U719, Paris; and Université Pierre et Marie Curie-Paris 6, Paris, France
- 2Cystic Fibrosis Association Vaincre la Mucoviscidose, Paris, France
- 3AP-HP, Hôpital Necker, Biostatistic Department, Paris; and Université René Descartes-Paris 5, Paris, France
- Correspondence to:
Dr B Fauroux
AP-HP, Hôpital Trousseau, Pediatric Pulmonary Department, Inserm, U719, Université Pierre et Marie Curie-Paris 6, 26 Avenue du Docteur Arnold Netter, 75571 Paris cedex 12, France; brigitte.fauroux{at}trs.aphp.fr
- Received 22 December 2005
- Accepted 31 May 2006
- Published Online First 29 June 2006
Abstract
Background: Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases. The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis.
Methods: A multicentre, randomised, double blind, placebo controlled trial was conducted from October 2001 to June 2003. The criteria for enrolment were age older than 6 years and forced expiratory volume in 1 second (FEV1) of 40% or more. The active group received either 250 mg or 500 mg (body weight < or ≥40 kg) of oral azithromycin three times a week for 12 months. The primary end point was change in FEV1.
Results: Eighty two patients of mean (SD) age 11.0 (3.3) years and mean (SD) FEV1 85 (22)% predicted were randomised: 40 in the azithromycin group and 42 in the placebo group. Nineteen patients were infected with Pseudomonas aeruginosa. The relative change in FEV1 at month 12 did not differ significantly between the two groups. The number of pulmonary exacerbations (count ratio 0.50 (95% CI 0.32 to 0.79), p<0.005), the time elapsed before the first pulmonary exacerbation (hazard ratio 0.37 (95% CI 0.22 to 0.63), p<0.0001), and the number of additional courses of oral antibiotics were significantly reduced in the azithromycin group regardless of the infectious status (count ratio 0.55 (95% CI 0.36 to 0.85), p<0.01). No severe adverse events were reported.
Conclusion: Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa.
Footnotes
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Published Online First 29 June 2006
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This study was supported by the Cystic Fibrosis Association Vaincre la Mucoviscidose, Paris, France.
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Competing interests: none declared.
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Investigators at clinical sites: M Roussey (Pediatric Department, Hôpital Sud, Rennes); J Navarro, A Munck, (Pediatric Department, Hôpital Robert Debré, Paris); I Pin (Pediatric Separtment, Hôpital de la Tronche, Grenoble); G Rault, V Storni (Pediatric Department, Centre de Perharidy, Roscoff); D Turck, D Wizla-Derambure (Pediatric Department, Hôpital Jeanne de Flandre, Lille); F Brémont (Pediatric Department, CHU Purpan, Toulouse); M Michaël Fayon (Pediatric Department, CHU Groupe Pellerin, Hôpital des Enfants, Bordeaux); P Gautry (Pediatric Department, CHG de Brive, Brive); L Delumley, J Languepin (Pediatric Department, CHU Dupuytren, Limoges); B Delaisi (Pediatric Pulmonology Center, Boulogne); V David (Pediatric Department, Hôpital Mère-Enfant, Nantes); A Sardet (Pediatric Department, Centre Hospitalier de Lens, Lens); C Marguet (Pediatric Department, CHU - Hôpital Charles Nicolle, Rouen); J C Dubus, L Mely (Pediatric Department, Hôpital d’Enfants de la Timone, Marseille); G A Loeuille (Pediatric Department, CHG de Dunkerque, Dunkerque); M Scalbert (Pediatric Department, Hôpital Saint-Antoine, Lille); P Blanchard (Pediatric Department, CHD Les Oudairies, La Roche sur Yon).
Data safety monitoring board: I Pin, Pediatric Deparment, University of Grenoble, Grenoble; D Turck, Pediatric Deparment, University of Lille, Lille.
Steering Committee: G Pons, Pharmacology Department, Hôpital St Vincent de Paul, Paris; E Jacqcz-Aigrain, Pharmacology Department, Hôpital R Debré, Paris; T Chinet, Pulmonology Deparment, Hôpital Ambroise Paré, Boulogne; I Durieu, Pulmonology Department, Hôpital Lyon Sud, Lyon.
