Improving outcomes of children and young adults with primary ciliary dyskinesia: a multi-centre, double-blind, double-dummy, 2x2 partial factorial, randomised controlled trial (REPEAT Study)
- National Health and Medical Research Council (NHMRC) Medical Research Futures Fund (MRFF)
- Queensland Children’s Hospital, Brisbane
- Royal Children’s Hospital, Melbourne
- Perth Children’s Hospital, Perth
- Royal Darwin Hospital, Darwin
- Concord Hospital, Sydney
- Among children and young adults with Primary Ciliary Dyskinesia (PCD), can acute respiratory exacerbations be reduced during 12 months of treatment with either:
a) Oral azithromycin (given 3 times a week) compared to placebo (equivalent volume); or
b) Oral erdosteine (given twice daily) compared to placebo (equivalent volume or capsule)?
- To determine the effects of 12 months of azithromycin or erdosteine on:
a) PCD-specific quality of life at 6 and 12 months and other secondary clinical outcomes (lung function, time to next exacerbation, hospitalisations);
b) Cost effectiveness; and
c) Nasopharyngeal bacterial carriage and antimicrobial resistance.
- To evaluate the effect of cilia ultrastructure (abnormality present/absent) on Aims-1 & 2a-b outcomes;
- To assess whether whole exome sequencing:
a) Is sensitive and specific in the identification of previously known gene mutations in PCD, and may identify new genes in cases who test negative;
b) Affects the diagnostic odyssey in PCD
PCD is a rare, incurable, progressive, serious disorder with a large unmet need in both the diagnosis & treatment. To date, all currently used therapies are unproven. PCD affects many organs particularly the lungs (causes bronchiectasis, respiratory failure & early mortality). Diagnosing PCD is complex, and the diagnosis is often delayed (~6yrs). PCD, a multi-gene heterogeneous disorder; incidence of ~1 in 20,000 live births.
The unmet needs of people with bronchiectasis are huge, with relatively few randomised controlled trials (RCTs). Bronchiectasis is deemed by the European Respiratory Society to be one of the most neglected lung diseases in current clinical practice. However, the unmet need for those with PCD (one of the many causes of bronchiectasis) is even larger.
Our RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) antibiotic (azithromycin and a novel mucolytic (erdosteine).
Implications for policy and practice:
Results will lead to the first-ever PCD-specific proven therapies, improved diagnostics, QoL and health outcomes for people with PCD.
For more information about the project contact Dr Gabrielle McCallum via email.
The project commenced in 2019 and is due to be completed in 2024.