Prednisone in Cystic Fibrosis Pulmonary Exacerbations

Study Overview
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Brief Summary
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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.

Official Title
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Randomized Controlled Trial of Prednisone in Cystic Fibrosis Pulmonary Exacerbations

Conditions
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Cystic Fibrosis Pulmonary Exacerbation

Intervention / Treatment
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* Drug: Prednisone
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CF by newborn screening or at least one clinical feature of CF, AND either (a) or (b) as follows: A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis A genotype with two identifiable CF-causing mutations Age > 6 years old. Acute pulmonary exacerbation treated with IV antibiotics as previously defined 10% relative drop in FEV1 from baseline at the time of exacerbation Informed consent by patient or parent/legal guardian Ability to reproducibly perform pulmonary function testing 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: A respiratory tract culture positive for Burkholderia cenocepacia in the 12 months prior to enrollment A respiratory tract culture positive for Mycobacterium abscessus in the 12 months prior to enrollment Treatment with IV or oral corticosteroids within 2 weeks of enrollment or from Day 0-Day 7 of the pulmonary exacerbation Active allergic bronchopulmonary aspergillosis (ABPA) at the time of enrollment as determined by treating physician Asthma related exacerbation at enrollment as defined by the treating physician based on clinically compatible symptoms (eg. wheeze) History of avascular necrosis or pathologic bone fracture Uncontrolled hypertension with end organ damage Active gastrointestinal bleeding Status post lung or other organ transplantation Pregnancy Lactose intolerance (contained in placebo) On Lumacaftor-Ivacaftor (Orkambi) at the time of exacerbation Investigational drug use within 30 days prior to enrollment visit Physical findings that would compromise the safety of the subject or the quality of the study data as determined by site investigator
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized placebo controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo<br>Placebo | Drug: Placebos<br>* Placebo<br>|
| Active Comparator: Treatment<br>Prednisone | Drug: Prednisone<br>* oral prednisone for 7 days during pulmonary exacerbation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung function recovery | 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. | At 14 days of antibiotic therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lung function recovery at follow up visit | The proportion of subjects who achieve >90% of their baseline FEV1 % predicted | 1 month follow up | 
| change in pulmonary function testing | change in pulmonary function testing | at day 7, 14 and 1 month follow up | 
| quality of life as measured by CFQ-R questionnaire | quality of life | at day 7, 14 and 1 month follow up | 
| quality of life as measured by CF Respiratory Symptom Diary | quality of life | at day 7, 14 and 1 month follow up | 
| length of hospitalization | length of hospitalization | Through study completion, up to 100 weeks | 
| time to subsequent pulmonary exacerbation | time to subsequent pulmonary exacerbation | 1 year follow up time | 
| number of adverse events | number of adverse events | At day day 14 of antibiotic therapy and 1 month follow up | 
| change in sputum inflammatory markers | change in sputum inflammatory markers | at day 7, 14 and 1 month follow up | 
| change in serum inflammatory markers | change in serum inflammatory markers | at day 7, 14 and 1 month follow up | 
| Duration of antibiotic treatment | Duration of antibiotic treatment | Through study completion, up to 100 weeks |