Talissa A Altes1, Mac Johnson2, Meredith Fidler3, Martyn Botfield4, Nicholas J Tustison5, Carlos Leiva-Salinas6, Eduard E de Lange7, Deborah Froh8, John P Mugler9. 1. Department of Radiology, One Hospital Drive, University of Missouri, Columbia, MO 65212, USA. Electronic address: altest@health.missouri.edu. 2. Vertex Pharmaceuticals Incorporated, 50 Northern Ave Boston, MA 02210, USA. Electronic address: mac_johnson@vrtx.com. 3. Vertex Pharmaceuticals Incorporated, 50 Northern Ave Boston, MA 02210, USA. Electronic address: meredith_fidler@vrtx.com. 4. Vertex Pharmaceuticals Incorporated, 50 Northern Ave Boston, MA 02210, USA. Electronic address: martynbotfield@gmail.com. 5. University of Virginia, 480 Ray C. Hunt Drive, Snyder Building, Office 124, Charlottesville, VA 22903, USA. Electronic address: ntustison@gmail.com. 6. University of Virginia, University Hospital, First Floor 1215 Lee St., Charlottesville, VA, 22908, USA. Electronic address: carlosleivasalinas@gmail.com. 7. University of Virginia, University Hospital, First Floor 1215 Lee St., Charlottesville, VA, 22908, USA. Electronic address: eed6s@virginia.edu. 8. University of Virginia, 100 Hospital Dr #5408, Charlottesville, VA 22903, USA. Electronic address: dkf2x@virginia.edu. 9. University of Virginia, Snyder Translational Research Building - Room 154, 480 Ray C. Hunt Drive, Charlottesville, VA 22903, USA. Electronic address: jpm7r@virginia.edu.
Abstract
BACKGROUND: This pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized 3He-magnetic resonance imaging (MRI)-defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D-CFTR mutation. METHODS: Part A (single-blind) comprised 4weeks of ivacaftor treatment; Part B (open-label) comprised 48weeks of treatment. The primary outcome was change from baseline in total ventilation defect (TVD; total defect volume:total lung volume ratio). RESULTS: Mean change in TVD ranged from -8.2% (p=0.0547) to -12.8% (p=0.0078) in Part A (n=8) and -6.3% (p=0.1953) to -9.0% (p=0.0547) in Part B (n=8) as assessed by human reader and computer algorithm, respectively. CONCLUSIONS: TVD responded to ivacaftor therapy. 3He-MRI provides an individual quantification of disease burden that may be able to detect aspects of the disease missed by population-based spirometry metrics. Assessments by human reader and computer algorithm exhibit similar trends, but the latter appears more sensitive. www.clinicaltrials.gov identifier: NCT01161537.
BACKGROUND: This pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized 3He-magnetic resonance imaging (MRI)-defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D-CFTR mutation. METHODS: Part A (single-blind) comprised 4weeks of ivacaftor treatment; Part B (open-label) comprised 48weeks of treatment. The primary outcome was change from baseline in total ventilation defect (TVD; total defect volume:total lung volume ratio). RESULTS: Mean change in TVD ranged from -8.2% (p=0.0547) to -12.8% (p=0.0078) in Part A (n=8) and -6.3% (p=0.1953) to -9.0% (p=0.0547) in Part B (n=8) as assessed by human reader and computer algorithm, respectively. CONCLUSIONS: TVD responded to ivacaftor therapy. 3He-MRI provides an individual quantification of disease burden that may be able to detect aspects of the disease missed by population-based spirometry metrics. Assessments by human reader and computer algorithm exhibit similar trends, but the latter appears more sensitive. www.clinicaltrials.gov identifier: NCT01161537.
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