None listed
Conditions
Brief summary
Primary ciliary dyskinesia (PCD), is a rare, incurable, progressive, serious disorder with a large unmet need in both the diagnosis & treatment. We will test the benefits of a currently used (but unapproved for long term use in PCD) antibiotic (azithromycin) and a novel mucolytic (erdosteine). We plan a parallel, multicentre, double-blinded, double-dummy RCT. Our primary question is: Among children and adults with PCD, does azithromycin or erdosteine reduce acute respiratory exacerbations during 12-mo of treatment? Study sites are Sydney, Brisbane, Melbourne, Darwin, Perth. Our secondary aims are to: 2. Determine the effects of 12-months of the azithromycin or erdosteine on PCD-quality of life (QoL), its cost effectiveness and impact on bacterial type and antibiotic resistance 3. Assess whether whole exome sequencing (WES) can identify known and unknown gene mutations in PCD, and whether knowing this improves the patient's journey
Interventions
Azithromycin: Oral 10mg/kg/dose (max 500 mg/dose), 3x weekly for 12 months. Supplied as powder for suspension
Erdosteine: Oral twice daily doses for 12 months [<15 kg 2.5 mls/dose; 15-19 kg 5mls/dose; 20-30 kg 7.5ml/dose or one capsule; >30 kg 10ml/dose or one capsule]. For children weighing 30 kgs or less, this will be supplied as powder for suspension. For those >30 kgs, powder for suspension will be used in those unable to take capsules.
Adherence will be monitored by return of bottles/pack
Azithromycin: Oral 10mg/kg/dose (max 500 mg/dose), 3x weekly for 12 months. Supplied as powder for suspension Erdosteine: Oral twice daily doses for 12 months [<15 kg 2.5 mls/dose; 15-19 kg 5mls/dose; 20-30 kg 7.5ml/dose or one capsule; >30 kg 10ml/dose or one capsule]. For children weighing 30 kgs or less, this will be supplied as powder for suspension. For those >30 kgs, powder for suspension will be used in those unable to take capsules. Adherence will be monitored by return of bottles/packs. Start of medications may be staggered. Not all participants will be on both trial medications.
Sponsors
Menzies School of Health Research
Study design
Allocation
Randomised controlled trial
Intervention model
Factorial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
2 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Children or adults (aged 2-.65 years) 2. Known PCD (defined by genetics or through electron microscopy) or probable PCD defined as (a) chronic wet/productive cough and a PICADAR score of at least 5 with nasal nitric oxide measurement (nNO) less than 77 nL/min [or equivalent cut-offs] on 2 occasions (when nNO levels can be measured i.e. aged over 5 years) or (b) clinician assessment based on medical history 3. At least two exacerbations in the last 18 months or one hospitalisation for respiratory exacerbation in the last 18 months; AND 4. Plan to remain at one of the study sites for at least 15 months
Exclusion criteria
1. Cystic fibrosis 2. On regular azithromycin (within the last 8 weeks) but if a participant is too unstable off azithromycin (defined by the participant’s primary specialist), the participant may be enrolled and will just be allocated to the erdosteine/placebo component (1:1 allocation) 3. Past (last 6 months) or current infection with non-tuberculous mycobacteria 4. Contraindication for macrolide or erdosteine use (e.g. liver dysfunction, hypersensitivity, renal failure, deficiency of the cystathionine-synthetase enzyme, phenylketonuria, active peptic ulcer) 5. Pregnant, pregnancy planned (in next 12 months) or nursing mothers 6. Abnormal ECG (QTc over 460 msec) or history of cardiac arrhythmia 7. Previously randomised 8. Hospitalised in the last 4 weeks for respiratory instability
Outcome results
None listed