A randomized trial of oral prednisone for cystic fibrosis pulmonary exacerbation treatment

Valerie Waters; Michelle Shaw; Lucy Perrem; Bradley S Quon; Elizabeth Tullis; Melinda Solomon; Jonathan H Rayment; Annick Lavoie; Sze Man Tse; Patrick Daigneault; Lara Bilodeau; April Price; Michael Nicholson; Melanie Chin; Michael Parkins; Martha L McKinney; Julian S Tam; Sanja Stanojevic; Hartmut Grasemann; Felix Ratjen; PIPE Study Investigators

doi:10.1183/13993003.02278-2023

A randomized trial of oral prednisone for cystic fibrosis pulmonary exacerbation treatment

Eur Respir J. 2024 May 2:2302278. doi: 10.1183/13993003.02278-2023. Online ahead of print.

Authors

Valerie Waters^{1

2}, Michelle Shaw^{2

3}, Lucy Perrem⁴, Bradley S Quon⁵, Elizabeth Tullis⁶, Melinda Solomon³, Jonathan H Rayment⁷, Annick Lavoie⁸, Sze Man Tse⁹, Patrick Daigneault¹⁰, Lara Bilodeau¹¹, April Price¹², Michael Nicholson¹³, Melanie Chin¹⁴, Michael Parkins¹⁵, Martha L McKinney¹⁶, Julian S Tam¹⁷, Sanja Stanojevic¹⁸, Hartmut Grasemann^{2

3}, Felix Ratjen^{2

3}; PIPE Study Investigators

Affiliations

¹ Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada Valerie.waters@sickkids.ca.
² Translational Medicine, Hospital for Sick Children, University of Toronto, Toronto, Canada.
³ Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada.
⁴ Department of Respiratory Medicine, Children's Health Ireland, Dublin, Ireland.
⁵ Division of Respiratory Medicine, Department of Medicine, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
⁶ Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Canada.
⁷ Division of Respiratory Medicine, Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
⁸ Division of Respiratory Medicine and Critical Care, Department of Medicine, Hotel Dieu Hospital, Montreal, Quebec, Canada.
⁹ Division of Respiratory Medicine, Department of Pediatrics, Centre Hospitalier Universitaire Sainte- Justine, Montreal, Quebec, Canada.
¹⁰ Division of Respiratory Medicine, Department of Pediatrics, Centre Hospitalier de l'Université de Quebec, Quebec, Quebec, Canada.
¹¹ Division of Respiratory Medicine, Department of Medicine, Institut de l'Université de Cardiologie et Pneumologie de Quebec, Quebec, Quebec, Canada.
¹² Division of Respiratory Medicine, Department of Pediatrics, London Health Sciences Centre, London, Ontario, Canada.
¹³ Division of Respiratory Medicine, Department of Medicine, London Health Sciences Centre, London, Ontario, Canada.
¹⁴ Division of Respiratory Medicine, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, Canada.
¹⁵ Division of Respiratory Medicine, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁶ Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, CA, USA.
¹⁷ Division of Respirology, Critical Care and Sleep Medicine, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
¹⁸ Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.

PMID: 38697648
DOI: 10.1183/13993003.02278-2023

Abstract

Background: Elevated markers of systemic and pulmonary inflammation are associated with failure to recover lung function following pulmonary exacerbations (PExs) in people with cystic fibrosis (pwCF). Our aim was to determine whether adjuvant oral prednisone treatment would improve recovery of forced expiratory volume in 1 second (ppFEV₁) in CF PExs not responding to antibiotic therapy.

Methods: This was a randomized, double-blind, placebo-controlled trial in pwCF treated with intravenous (IV) antibiotics for a PEx. At Day 7, those who had not returned to >90% baseline ppFEV₁ were randomized to adjuvant prednisone 1 mg·kg^-1 twice daily (max 60 mg/day) or placebo for 7 days. The primary outcome was the difference in proportion of subjects who recovered >90% baseline ppFEV₁ at Day 14 of IV antibiotic therapy.

Results: 173 subjects were enrolled, with 76 randomized. 50% of subjects in the prednisone group recovered baseline FEV₁ on Day 14 compared to 39% of subjects in the placebo group for a difference of 11% (95% CI -11, 34%, p=0.34). The mean (sd) change in ppFEV₁ from Day 7 to Day 14 was 6.8% predicted (8.8) in the prednisone group and 4.6% (6.9) in the placebo group (mean difference 2.2% predicted 95% CI -1.5, 5.9%, p=0.24). Time to subsequent exacerbation was not prolonged in prednisone treated subjects (HR 0.83, 95% CI 0.45, 1.53; p=0.54).

Conclusions: This study failed to detect a difference in ppFEV₁ recovery between adjuvant oral prednisone and placebo treatment in pwCF not responding at day 7 of IV antibiotic therapy for PExs.