Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study |
| |
| Authors: | Vivian Phan Jared Hershenson Laura Caldarera Sandra K Larkin Kari Wheeler Ana Lucia Cortez Robin Dulman Noravy Briere Angela Lewis Frans A Kuypers Elizabeth Yang |
| |
| Institution: | 1. Hematology-Oncology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA;2. Division of Cardiology, Children's National Hospital, Washington, District of Columbia, USA;3. Child Cardiology Associates, Rockville, Maryland, USA
Died early 2022.;4. Department of Pediatrics, University of California San Francisco, Oakland, California, USA;5. Inova Fairfax Children's Hospital, Falls Church, Virginia, USA |
| |
| Abstract: | Background Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA. Methods In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2. Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected. Results Ten hemoglobin SS patients aged 12–24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P50 left shift of average −11 mmHg (p < .0001) with decreased oxygen off-loading at low pO2. The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from −12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive. Conclusion In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients. |
| |
| Keywords: | cardiopulmonary test exercise oxygen dissociation curve peak VO2 sickle cell voxelotor |
|
|
