The University of Southampton
University of Southampton Institutional Repository

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

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
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
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).
1471-2466
1-11
Kobbernagel, Helene E.
194e2202-c935-4462-a73a-e69dd776cdea
Buchvald, Frederik F.
8059843a-30a8-4d79-8b99-a8f476d3fa57
Haarman, Eric G.
953b1ca1-3218-435c-9a0e-32e7b2d95798
Casaulta, Carmen
0a57a56c-3780-4fd4-a616-2e1348742348
Collins, Samuel A.
3c35238c-dbbd-4021-b7fa-c5b89e471981
Hogg, Claire
78881fd2-dbe9-4c28-b050-3387c163df1e
Kuehni, Claudia E.
ac67c925-ee32-429d-a3b5-c244daa314b4
Omran, Heymut
49c453b0-2ce2-4925-b5d4-7beffe2bae8d
Lucas, Jane S.
5cb3546c-87b2-4e59-af48-402076e25313
Quittner, Alexandra L.
c0f8318e-574d-4766-8154-6f055eba45ea
Werner, Claudius
4179e6c9-6cf3-4e9a-802f-de64cf1fbd72
Nielsen, Kim G.
9f6ba945-07cd-4ecc-81f3-87d645a17a8b
Kobbernagel, Helene E.
194e2202-c935-4462-a73a-e69dd776cdea
Buchvald, Frederik F.
8059843a-30a8-4d79-8b99-a8f476d3fa57
Haarman, Eric G.
953b1ca1-3218-435c-9a0e-32e7b2d95798
Casaulta, Carmen
0a57a56c-3780-4fd4-a616-2e1348742348
Collins, Samuel A.
3c35238c-dbbd-4021-b7fa-c5b89e471981
Hogg, Claire
78881fd2-dbe9-4c28-b050-3387c163df1e
Kuehni, Claudia E.
ac67c925-ee32-429d-a3b5-c244daa314b4
Omran, Heymut
49c453b0-2ce2-4925-b5d4-7beffe2bae8d
Lucas, Jane S.
5cb3546c-87b2-4e59-af48-402076e25313
Quittner, Alexandra L.
c0f8318e-574d-4766-8154-6f055eba45ea
Werner, Claudius
4179e6c9-6cf3-4e9a-802f-de64cf1fbd72
Nielsen, Kim G.
9f6ba945-07cd-4ecc-81f3-87d645a17a8b

Kobbernagel, Helene E., Buchvald, Frederik F., Haarman, Eric G., Casaulta, Carmen, Collins, Samuel A., Hogg, Claire, Kuehni, Claudia E., Omran, Heymut, Lucas, Jane S., Quittner, Alexandra L., Werner, Claudius and Nielsen, Kim G. (2016) 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. BMC Pulmonary Medicine, 16 (104), 1-11. (doi:10.1186/s12890-016-0261-x). (PMID:27450411)

Record type: 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).

Text
art_10.1186_s12890-016-0261-x.pdf - Version of Record
Available under License Creative Commons Attribution.
Download (636kB)
Text
index.html - Other
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 25 June 2016
e-pub ahead of print date: 22 July 2016
Published date: 22 July 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 399374
URI: https://eprints.soton.ac.uk/id/eprint/399374
ISSN: 1471-2466
PURE UUID: c2c45a5b-aba8-44b9-a4ca-024c9040622e

Catalogue record

Date deposited: 15 Aug 2016 10:55
Last modified: 02 Dec 2019 20:01

Export record

Altmetrics

Contributors

Author: Helene E. Kobbernagel
Author: Frederik F. Buchvald
Author: Eric G. Haarman
Author: Carmen Casaulta
Author: Samuel A. Collins
Author: Claire Hogg
Author: Claudia E. Kuehni
Author: Heymut Omran
Author: Jane S. Lucas
Author: Alexandra L. Quittner
Author: Claudius Werner
Author: Kim G. Nielsen

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×