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.
- Kobbernagel HE Danish Paediatric Pulmonary Service, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
- Buchvald FF Danish Paediatric Pulmonary Service, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
- Haarman EG Department of Pediatric Pulmonology, VU University Medical Center, Amsterdam, Netherlands.
- Casaulta C Division of Respiratory Medicine, Department of Pediatrics, Inselspital and University of Bern, Bern, Switzerland.
- Collins SA PCD Centre, NIHR Respiratory Biomedical Research Unit and Wellcome Trust Clinical Research Facility, University of Southampton, Southampton, UK.
- Hogg C Paediatric Respiratory Department, Royal Brompton Hospital, London, UK.
- Kuehni CE Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
- Lucas JS PCD Centre, NIHR Respiratory Biomedical Research Unit and Wellcome Trust Clinical Research Facility, University of Southampton, Southampton, UK.
- Omran H Department of General Paediatrics, University Children's Hospital Muenster, Muenster, Germany.
- Quittner AL Department of Psychology, University of Miami, Coral Gables, Florida, USA.
- Werner C Department of General Paediatrics, University Children's Hospital Muenster, Muenster, Germany.
- Nielsen KG Danish Paediatric Pulmonary Service, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. kgn@dadlnet.dk.
- 2016-07-25
Published in:
- BMC pulmonary medicine. - 2016
Azithromycin
Exacerbation
Health-related quality of life
Lung clearance index
Multiple breath washout
Primary ciliary dyskinesia
QOL-PCD
Adolescent
Adult
Anti-Bacterial Agents
Azithromycin
Child
Disease Progression
Double-Blind Method
Europe
Female
Humans
Kartagener Syndrome
Male
Middle Aged
Quality of Life
Regression Analysis
Research Design
Respiratory Tract Infections
Spirometry
Treatment Outcome
Vital Capacity
Young Adult
English
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).
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).
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s12890-016-0261-x
- PMID 27450411
- Persistent URL
- https://sonar.ch/global/documents/278568
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