Cystic Fibrosis Pulmonary Exacerbation
Conditions
Brief summary
This will be a 5 year randomized, double blind, placebo controlled trial of 7 days of oral prednisone in cystic fibrosis (CF) patients receiving intravenous (IV) antibiotic treatment for a pulmonary exacerbation at the Hospital for Sick Children and other study sub-sites across Canada. The intervention will be oral prednisone 2 mg/kg/day (max 60 mg) divided twice daily for 7 days as an adjunctive therapy for pulmonary exacerbations in CF patients who have not recovered their baseline forced expiratory volume in 1 second (FEV1) after 7 days of IV antibiotic treatment. The primary outcome will be the proportion of subjects who achieve \>90% of their baseline FEV1 % predicted at day 14 of IV antibiotic treatment for a pulmonary exacerbation in each treatment arm.
Interventions
DRUGPrednisone
oral prednisone for 7 days during pulmonary exacerbation
DRUGPlacebos
Placebo
Sponsors
Canadian Cystic Fibrosis Foundation
The Hospital for Sick Children
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
placebo
Intervention model description
Randomized placebo controlled trial
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of CF by newborn screening or at least one clinical feature of CF, AND either (a) or (b) as follows: 2. A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis 3. A genotype with two identifiable CF-causing mutations 4. Age \> 6 years old. 5. Acute pulmonary exacerbation treated with IV antibiotics as previously defined 10% relative drop in FEV1 from baseline at the time of exacerbation 6. Informed consent by patient or parent/legal guardian 7. Ability to reproducibly perform pulmonary function testing 8. Ability to comply with medication use including the ability to take capsules, study visits and study procedures as judged by the site investigator
Exclusion criteria
1. A respiratory tract culture positive for Burkholderia cenocepacia in the 12 months prior to enrollment 2. A respiratory tract culture positive for Mycobacterium abscessus in the 12 months prior to enrollment 3. Treatment with IV or oral corticosteroids within 2 weeks of enrollment or from Day 0-Day 7 of the pulmonary exacerbation 4. Active allergic bronchopulmonary aspergillosis (ABPA) at the time of enrollment as determined by treating physician 5. Asthma related exacerbation at enrollment as defined by the treating physician based on clinically compatible symptoms (eg. wheeze) 6. History of avascular necrosis or pathologic bone fracture 7. Uncontrolled hypertension with end organ damage 8. Active gastrointestinal bleeding 9. Status post lung or other organ transplantation 10. Pregnancy 11. Lactose intolerance (contained in placebo) 12. On Lumacaftor-Ivacaftor (Orkambi) at the time of exacerbation 13. Investigational drug use within 30 days prior to enrollment visit 14. Physical findings that would compromise the safety of the subject or the quality of the study data as determined by site investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lung function recovery | At 14 days of antibiotic therapy | The proportion of subjects who achieve \>90% of their baseline FEV1 % predicted at day 14 of IV antibiotic treatment for a PEx in each treatment arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| change in pulmonary function testing | at day 7, 14 and 1 month follow up | change in pulmonary function testing |
| quality of life as measured by CFQ-R questionnaire | at day 7, 14 and 1 month follow up | quality of life |
| quality of life as measured by CF Respiratory Symptom Diary | at day 7, 14 and 1 month follow up | quality of life |
| length of hospitalization | Through study completion, up to 100 weeks | length of hospitalization |
| lung function recovery at follow up visit | 1 month follow up | The proportion of subjects who achieve \>90% of their baseline FEV1 % predicted |
| number of adverse events | At day day 14 of antibiotic therapy and 1 month follow up | number of adverse events |
| change in sputum inflammatory markers | at day 7, 14 and 1 month follow up | change in sputum inflammatory markers |
| change in serum inflammatory markers | at day 7, 14 and 1 month follow up | change in serum inflammatory markers |
| Duration of antibiotic treatment | Through study completion, up to 100 weeks | Duration of antibiotic treatment |
| time to subsequent pulmonary exacerbation | 1 year follow up time | time to subsequent pulmonary exacerbation |
Countries
Canada
Outcome results
None listed