Table 2. Primary and Secondary Functional Efficacy End Points in a Study of the Effect of Praliciguat on Peak Rate of Oxygen Consumption (V̇o2) in Patients With Heart Failure With Preserved Ejection Fractiona.
| End point | 40-mg praliciguat group (n = 65) | Placebo group (n = 78) | Adjusted difference in difference (95% CI)b | P value | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Mean (SD) | Absolute difference (SD) | Adjusted difference (95% CI)b | Mean (SD) | Absolute difference (SD) | Adjusted difference (95% CI)b | |||||
| Baseline | Week 12 | Baseline | Week 12 | |||||||
| Primary | (n = 64) | (n = 72) | ||||||||
| Peak V̇o2, mL/kg/minc | 13.2 (4.1) | 12.9 (3.9) | −0.3 (2.1) | −0.3 (−0.8 to 0.3) | 12.8 (3.5) | 12.9 (3.8) | 0.1 (1.8) | 0.04 (−0.5 to 0.6) | −0.3 (−1.0 to 0.4) | .37 |
| Secondary | Nominal P value | |||||||||
| 6-min walk test distance, md | (n = 63) | (n = 72) | ||||||||
| 333.5 (128.2) | 339.9 (144.4) | 6.4 (82.2) | 41.4 (8.3 to 74.5) | 314.5 (128.5) | 341.4 (125.4) | 27.0 (105.2) | 58.1 (26.1 to 90.1) | −16.7 (−47.4 to 13.9) | .28 | |
| Ventilatory efficiency, VE/VCo2 slopee | (n = 64) | (n = 72)c | ||||||||
| 31.6 (6.9) | 31.4 (6.4) | −0.2 (3.8) | 0.3 (−1.1 to 1.7) | 30.8 (7.2) | 31.1 (7.8) | 0.3 (3.9) | 0.6 (−0.8 to 1.9) | −0.3 (−1.6 to 1.0) | .65 | |
| CPET responders, No. (%)f | (n = 65) | (n = 78) | ||||||||
| 13 (20.0) | 17 (21.8) | Odds ratio, 0.9 (0.4 to 2.1) | .82 | |||||||
| Planned subgroup analysis | (n = 56) | (n = 62) | Nominal P value | |||||||
| Peak V̇o2 in patients without atrial fibrillation, mL/kg/min | (n = 55) | (n = 59) | ||||||||
| 13.4 (4.0) | 13.0 (4.0) | −0.4 (2.1) | −0.3 (−0.9 to 0.2) | 12.8 (3.6) | 12.9 (4.0) | 0.1 (1.8) | 0.1 (−0.4 to 0.6) | −0.4 (−1.1 to 0.3) | .28 | |
Abbreviation: VE/VCo2, ventilation/carbon dioxide production.
Data are for the primary analytic population (all patients who completed 8 weeks of dosing, had at least 1 evaluable postbaseline assessment, and did not have a dose reduction or major protocol deviations). Change from baseline analysis for an end point included patients with measurements at both baseline and week 12 for that specific end point. Cardiopulmonary exercise test (CPET) responder analyses considered patients who were hospitalized or died due to heart failure or had missing assessments performed after the participant received their first dose of the study drug as nonresponders.
Adjusted treatment differences are estimates from an analysis of covariance model with treatment group and stratification factors as categorical variable terms and baseline value as a covariate. CPET responders were analyzed using a Cochran-Mantel-Haenszel test controlling for treatment group and stratification factors.
Normal values vary by age and sex, with higher values representing better functional capacity.
An increase (positive value) denotes improvement and a decrease (negative value) denotes worsening.
Ventilatory efficiency is a unitless index that is defined by minute ventilation (in L/min) relative to carbon dioxide production (in L/min) throughout exercise. Higher values represent worse efficiency.
Patients who improved by at least 1.5 mL/kg/min in peak V̇o2 from baseline to week 12.