Prednisone in Cystic Fibrosis Pulmonary Exacerbations (PIPE)

Randomized Controlled Trial of Prednisone in Cystic Fibrosis Pulmonary Exacerbations

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis Pulmonary Exacerbation
• Intervention / Treatment: Drug: Placebos; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • The Governers of The University of Calgary - Alberta Health Services
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
    • Vancouver, British Columbia, Canada, V6H 3N1
      • British Columbia Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6C 2R5
      • London Health Sciences Centre - Lawson Health Research Institute
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • Unity Health Toronto - St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G1X8
      • SickKids
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • Centre Hospitalier Universitaire Sainte-Justine
    • Montréal, Quebec, Canada, H2X A09
      • The Centre hospitalier de l'Université de Montréal (CHUM)
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHU de Quebec-Universite Laval
    • Quebec City, Quebec, Canada, G1V 4G5
      • Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • University of Saskatchewan - Saskatchewan Health Authority

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo	Drug: Placebos; Placebo
Active Comparator: Treatment; Prednisone	Drug: Prednisone; oral prednisone for 7 days during pulmonary exacerbation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: Canadian Cystic Fibrosis Foundation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): October 7, 2023
• Study Completion (Actual): October 7, 2023

Study Registration Dates

• First Submitted: February 8, 2017
• First Submitted That Met QC Criteria: February 28, 2017
• First Posted (Actual): March 3, 2017

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: REB1000053825

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No