Table 2.
Endpoints
| Primary endpoint |
| Change in peak V̇O2 from Week 0 (baseline) to Week 12 based on CPX |
| Secondary endpoint |
| Changes over time in peak V̇O2 (from Week 0 to Weeks 12 and 24) based on CPX |
| Exploratory endpoints |
| 1. Resting heart rate (12-lead electrocardiography) |
| 2. NYHA functional classification |
| 3. Plasma BNP concentration |
| 4. Blood pressure and pulse rate |
| 5. CPX parameters (other than peak V̇O2): |
| AT, RCP, heart rate (at rest, at the initiation of warm-up exercise, at the AT point, at the RCP point, at peak, at completion of cool-down exercise), R, V̇E/V̇CO2, V̇E/V̇O2, V̇E vs. V̇CO2 slope, PETCO2, PETO2, TV-RR relationship, RR threshold, Ti/Ttot, breathing reserve, SpO2, oscillatory ventilation, OUES, peak V̇O2/HR, work rate (watts), and V̇O2/HR jump-up phenomenon |
| 6. Echocardiographic parameters: |
| LVDd, LVDs, IVST, LVPWT, LVEDV, LVESV, LVEF, E/A, DT, E/e′, LAD, LA volume, RVSP, TAPSE, IVC diameter, mitral regurgitation (qualitative), and tricuspid regurgitation (qualitative) |
| 7. Grip strength measurement |
| 8. Quality of life survey |
| Safety endpoints |
| 1. Adverse events |
| 2. Risks specified in the risk management plan: |
| Important identified risks: bradycardia, photopsia and blurry vision, atrioventricular block, atrial fibrillation, and QT prolongation |
| Important potential risks: supraventricular tachyarrhythmia (excluding atrial fibrillation) and ventricular arrhythmia |
| 3. Blood testing: |
| Hematology: red blood cell count, hemoglobin level, white blood cell count, and platelet count |
| Blood biochemistry: total protein, albumin, urea nitrogen, creatinine, estimated glomerular filtration rate, total bilirubin, aspartate aminotransferase, alanine aminotransferase, sodium, potassium, and chloride |
| 4. 12-lead electrocardiography: heart rate, PQ, QRS, QT, and QTc |
AT, anaerobic threshold; BNP, B-type natriuretic peptide; CPX, cardiopulmonary exercise testing; DT, deceleration time of the E velocity; E/A, ratio of the E- and A-wave maximum velocities; E/e′, ratio of the E-wave maximum velocity and early diastolic velocities of the septal mitral annulus; IVC, inferior vena cava; IVST, interventricular septum thickness; LA, left atrial; LAD, left atrial diameter; LVDd, left ventricular diastolic dimension; LVDs, left ventricular diastolic dimension; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; LVPWT, left ventricular posterior wall thickness; NYHA, New York Heart Association; OUES, oxygen uptake efficiency slope; PETCO2, end-tidal carbon dioxide tension; PETO2, end-tidal oxygen tension; R, gas exchange ratio; RCP, respiratory compensation point; RR, respiratory rate; RVSP, right ventricular systolic pressure; SpO2, percutaneous oxygen saturation; TAPSE, tricuspid annular plane systolic excursion; Ti/Ttot, ratio of inspiratory time to total respiratory cycle time; TV, tidal volume; V̇E vs. CO2 slope, minute ventilation vs. carbon dioxide production slope; V̇E/V̇CO2, ventilatory equivalent for carbon dioxide; V̇E/V̇O2, ventilatory equivalent for oxygen; V̇O2, oxygen uptake; V̇O2/HR, oxygen pulse.