Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

Stephanie D Davis; Felix Ratjen; Lyndia C Brumback; Robin C Johnson; Amy G Filbrun; Gwendolyn S Kerby; Howard B Panitch; Scott H Donaldson; Margaret Rosenfeld; ISIS Study Group

doi:10.1016/j.jcf.2015.10.007

Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis

J Cyst Fibros. 2016 May;15(3):386-91. doi: 10.1016/j.jcf.2015.10.007. Epub 2015 Nov 4.

Authors

Stephanie D Davis¹, Felix Ratjen², Lyndia C Brumback³, Robin C Johnson⁴, Amy G Filbrun⁵, Gwendolyn S Kerby⁶, Howard B Panitch⁷, Scott H Donaldson⁸, Margaret Rosenfeld⁹; ISIS Study Group

Affiliations

¹ Section of Pediatric Pulmonology, Allergy and Sleep Medicine, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA.
² Division of Respiratory Medicine, Department of Pediatrics, the Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
³ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁴ Division of Pediatric Pulmonology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Pediatric Pulmonary Division, Department of Pediatrics, CS Mott Children's Hospital, University of Michigan School of Medicine, Ann Arbor, MI, USA.
⁶ Department of Pediatrics, The Breathing Institute, University of Colorado and Children's Hospital, Aurora, CO, USA.
⁷ Division of Pulmonary Medicine, Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁸ Division of Pulmonary and Critical Care, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁹ Division of Pulmonary Medicine, Seattle Children's Hospital and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.

Abstract

Background: The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint.

Methods: Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials.

Results: Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0).

Conclusions: iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials.

Keywords: FEV; Forced expiratory flow rates; Pulmonary function tests.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cystic Fibrosis* / diagnosis
Cystic Fibrosis* / physiopathology
Dimensional Measurement Accuracy
Female
Forced Expiratory Volume*
Humans
Infant
Lung / physiopathology*
Male
Respiratory Function Tests / methods*
Sodium Chloride / pharmacology

Substances

Sodium Chloride

Abstract

Publication types

MeSH terms

Substances

Grants and funding