Clinical trial NCT03070522: Prednisone in Cystic Fibrosis Pulmonary Exacerbations
Official title: Randomized Controlled Trial of Prednisone in Cystic Fibrosis Pulmonary Exacerbations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis Pulmonary Exacerbation
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Canadian Cystic Fibrosis Foundation
First posted: 2017-03-03
Enrollment: 76
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized placebo controlled trial
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Lung function recovery
timeFrame: At 14 days of antibiotic therapy
Secondary outcomes:
measure: lung function recovery at follow up visit
timeFrame: 1 month follow up
measure: change in pulmonary function testing
timeFrame: at day 7, 14 and 1 month follow up
measure: quality of life as measured by CFQ-R questionnaire
timeFrame: at day 7, 14 and 1 month follow up
measure: quality of life as measured by CF Respiratory Symptom Diary
timeFrame: at day 7, 14 and 1 month follow up
measure: length of hospitalization
timeFrame: Through study completion, up to 100 weeks
measure: time to subsequent pulmonary exacerbation
timeFrame: 1 year follow up time
measure: number of adverse events
timeFrame: At day day 14 of antibiotic therapy and 1 month follow up
measure: change in sputum inflammatory markers
timeFrame: at day 7, 14 and 1 month follow up
measure: change in serum inflammatory markers
timeFrame: at day 7, 14 and 1 month follow up
measure: Duration of antibiotic treatment
timeFrame: Through study completion, up to 100 weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: The Governers of The University of Calgary - Alberta Health Services
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre - Lawson Health Research Institute
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Unity Health Toronto - St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: SickKids
state: Ontario
city: Montréal
country: Canada
facility: The Centre hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: Centre hospitalier universitaire Sainte-Justine
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec-Universite Laval
state: Quebec
city: Quebec City
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
state: Quebec
city: Saskatoon
country: Canada
facility: University of Saskatchewan - Saskatchewan Health Authority
state: Saskatchewan
Study officials:
References:
citation: Waters V, Shaw M, Perrem L, Quon BS, Tullis E, Solomon M, Rayment JH, Lavoie A, Tse SM, Daigneault P, Bilodeau L, Price A, Nicholson M, Chin M, Parkins M, McKinney ML, Tam JS, Stanojevic S, Grasemann H, Ratjen F; (PIPE Study Investigators). A randomised trial of oral prednisone for cystic fibrosis pulmonary exacerbation treatment. Eur Respir J. 2024 Jun 6;63(6):2302278. doi: 10.1183/13993003.02278-2023. Print 2024 Jun.