Study protocol, rationale and recruitment in a European multi-centre randomized controlled trial to determine the efficacy and safety of azithromycin maintenance therapy for 6 months in primary ciliary dyskinesia
Author(s)
Type
Journal Article
Abstract
Background: Clinical management of primary ciliary dyskinesia (PCD) respiratory disease is currently based on improving
mucociliary clearance and controlling respiratory infections, through the administration of antibiotics. Treatment practices
in PCD are largely extrapolated from more common chronic respiratory disorders, particularly cystic fibrosis, but
no randomized controlled trials (RCT) have ever evaluated efficacy and safety of any pharmacotherapeutics used
in the treatment of PCD. Maintenance therapy, with the macrolide antibiotic azithromycin, is currently widely used in
chronic respiratory diseases including PCD. In addition to its antibacterial properties, azithromycin is considered to have
beneficial anti-inflammatory and anti-quorum-sensing properties.
The aim of this study is to determine the efficacy of azithromycin maintenance therapy for 6 months on respiratory
exacerbations in PCD. The secondary objectives are to evaluate the efficacy of azithromycin on lung function, ventilation
inhomogeneity, hearing impairment, and symptoms (respiratory, sinus, ears and hearing) measured on a PCD-specific
health-related quality of life instrument, and to assess the safety of azithromycin maintenance therapy in PCD.
Methods: The BESTCILIA trial is a European multi-centre, double-blind, randomized, placebo-controlled, parallel group
study. The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three
times a week for 6 months. Subjects with a confirmed diagnosis of PCD, age 7–50 years, are eligible for inclusion.
Chronic pulmonary infections with Gram-negative bacteria or any recent occurrence of non-tuberculous mycobacteria
are exclusion criteria. The planned number of subjects to be included is 125. The trial has been approved by the
Research Ethics Committees of the participating institutions. Discussion: We present a study protocol of an ongoing RCT, evaluating for the first time, the efficacy and safety of a
pharmacotherapeutic treatment for patients with PCD. The RCT evaluates azithromycin maintenance therapy, a drug
already commonly prescribed in other chronic respiratory disorders. Furthermore, the trial will utilize the Lung clearance
index and new, PCD-specific quality of life instruments as outcome measures for PCD. Recruitment is hampered
by frequent occurrence of Pseudomonas aeruginosa infection, exacerbations at enrolment, and the patients’
perception of disease severity and necessity of additional management and treatment during trial participation.
Trial registration: EudraCT 2013-004664-58 (date of registration: 2014-04-08).
mucociliary clearance and controlling respiratory infections, through the administration of antibiotics. Treatment practices
in PCD are largely extrapolated from more common chronic respiratory disorders, particularly cystic fibrosis, but
no randomized controlled trials (RCT) have ever evaluated efficacy and safety of any pharmacotherapeutics used
in the treatment of PCD. Maintenance therapy, with the macrolide antibiotic azithromycin, is currently widely used in
chronic respiratory diseases including PCD. In addition to its antibacterial properties, azithromycin is considered to have
beneficial anti-inflammatory and anti-quorum-sensing properties.
The aim of this study is to determine the efficacy of azithromycin maintenance therapy for 6 months on respiratory
exacerbations in PCD. The secondary objectives are to evaluate the efficacy of azithromycin on lung function, ventilation
inhomogeneity, hearing impairment, and symptoms (respiratory, sinus, ears and hearing) measured on a PCD-specific
health-related quality of life instrument, and to assess the safety of azithromycin maintenance therapy in PCD.
Methods: The BESTCILIA trial is a European multi-centre, double-blind, randomized, placebo-controlled, parallel group
study. The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three
times a week for 6 months. Subjects with a confirmed diagnosis of PCD, age 7–50 years, are eligible for inclusion.
Chronic pulmonary infections with Gram-negative bacteria or any recent occurrence of non-tuberculous mycobacteria
are exclusion criteria. The planned number of subjects to be included is 125. The trial has been approved by the
Research Ethics Committees of the participating institutions. Discussion: We present a study protocol of an ongoing RCT, evaluating for the first time, the efficacy and safety of a
pharmacotherapeutic treatment for patients with PCD. The RCT evaluates azithromycin maintenance therapy, a drug
already commonly prescribed in other chronic respiratory disorders. Furthermore, the trial will utilize the Lung clearance
index and new, PCD-specific quality of life instruments as outcome measures for PCD. Recruitment is hampered
by frequent occurrence of Pseudomonas aeruginosa infection, exacerbations at enrolment, and the patients’
perception of disease severity and necessity of additional management and treatment during trial participation.
Trial registration: EudraCT 2013-004664-58 (date of registration: 2014-04-08).
Date Issued
2016-07-22
Date Acceptance
2016-06-25
Citation
BMC Pulmonary Medicine, 2016, 16
ISSN
1471-2466
Publisher
BioMed Central
Journal / Book Title
BMC Pulmonary Medicine
Volume
16
Copyright Statement
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Respiratory System
Primary ciliary dyskinesia
Azithromycin
Lung clearance index
Multiple breath washout
Health-related quality of life
QOL-PCD
Exacerbation
CYSTIC-FIBROSIS BRONCHIECTASIS
LUNG CLEARANCE INDEX
OF-THE-ART
PSEUDOMONAS-AERUGINOSA
CONSENSUS STATEMENT
DOUBLE-BLIND
CHILDREN
DISEASE
EXACERBATIONS
SPIROMETRY
Publication Status
Published
Article Number
104