Table 2:
Primary and Secondary Endpoints
| Dapagliflozin | Placebo | Estimated Treatment Differencea | ||||||
|---|---|---|---|---|---|---|---|---|
| Endpoint Classification | Measurement | Study Period | N | Mean (SD) | N | Mean (SD) | (95% CI) | P-value |
| Exercise | PCWP, mmHgb | Baseline | 21 | 33.5 (7.5) | 17 | 32.0 (5.8) | -- | -- |
| End of Study | 21 | 27.0 (6.8) | 16 | 30.8 (8.1) | -- | -- | ||
| Change from baseline | 21 | −6.6 (7.2) | 16 | −0.4 (8.4) | −5.7 (−10.8 to −0.7) | 0.027 | ||
| RA pressure, mmHgc | Baseline | 21 | 19.9 (7.0) | 17 | 18.2 (6.3) | -- | -- | |
| End of Study | 21 | 16.5 (6.8) | 16 | 18.7 (7.1) | -- | -- | ||
| Change from baseline | 21 | −3.4 (4.0) | 16 | 0.8 (5.6) | −4.1 (−7.2 to −1.0) | 0.011 | ||
| Mean PA pressure, mmHgd | Baseline | 21 | 49.9 (10.2) | 17 | 49.4 (10.6) | -- | -- | |
| End of Study | 21 | 44.7 (10.6) | 16 | 49.4 (10.6) | -- | -- | ||
| Change from baseline | 21 | −5.2 (6.6) | 16 | 0.7 (8.6) | −5.7 (−10.7 to −0.8) | 0.024 | ||
| Rest | PCWP, mmHgb | Baseline | 21 | 16.0 (3.9) | 17 | 15.8 (4.6) | -- | -- |
| End of Study | 21 | 13.5 (3.7) | 16 | 16.8 (5.5) | -- | -- | ||
| Change from baseline | 21 | −2.5 (3.7) | 16 | 1.1 (5.9) | −3.5 (−6.6 to −0.4) | 0.029 | ||
| RA pressure, mmHgc | Baseline | 21 | 10.4 (2.4) | 17 | 9.6 (3.2) | -- | -- | |
| End of Study | 21 | 8.8 (2.4) | 16 | 9.8 (3.6) | -- | -- | ||
| Change from baseline | 21 | −1.6 (2.6) | 16 | 0.3 (4.0) | −1.8 (−4.0 to −0.3) | 0.088 | ||
| Mean PA pressure, mmHgd | Baseline | 21 | 26.5 (6.9) | 17 | 26.2 (7.6) | -- | -- | |
| End | 21 | 24.7 (7.1) | 16 | 27.1 (6.1) | -- | -- | ||
| Change from baseline | 21 | −1.8 (4.0) | 16 | 1.1 (7.4) | −2.8 (−6.6 to 0.9) | 0.136 | ||
| Body weight, kg | Baseline | 21 | 100.8 (26.5) | 17 | 98.1 (18.2) | -- | -- | |
| End of Study | 21 | 97.1 (24.6) | 16 | 97.7 (18.8) | -- | -- | ||
| Change from baseline | 21 | −3.7 (4.2) | 16 | −0.2 (2.6) | −3.5 (−5.9 to −1.1) | 0.006 | ||
| Total blood volume, ml | Baseline | 21 | 5639 (1405) | 17 | 5533 (1088) | -- | -- | |
| Change from baseline | 21 | −118 (542) | 16 | 142 (399) | −259 (−586 to 68) | 0.12 | ||
| Red cell volume, ml | Baseline | 21 | 1859 (514) | 17 | 1889 (1709) | -- | -- | |
| End of Study | 21 | 1911 (468) | 16 | 1907 (422) | -- | -- | ||
| Change from baseline | 21 | 52 (285) | 16 | 26 (129) | 26 (−130 to 182) | 0.73 | ||
| Plasma volume, ml | Baseline | 21 | 3779 (946) | 17 | 3643 (755) | -- | -- | |
| End of Study | 21 | 3609 (889) | 16 | 3759 (712) | -- | -- | ||
| Change from baseline | 21 | −170 (343) | 16 | 115 (322) | −285 (−510 to −60) | 0.014 |
The treatment effect is estimated using a repeated measures mixed model that included repeated measures for baseline and end of study. For outcomes measured at rest and peak exercise intensity, a single model with 8 estimated means was constructed (i.e., 2 treatment groups (Dapagliflozin, placebo) × 2 measurement times (baseline, end of study) × 2 e×ercise levels (peak, rest)). For the remaining secondary outcomes, the model estimated only four means (2 treatment groups × 2 measurement times). A model-based contrast was used to estimate the treatment effect which was defined as the difference in the changes from baseline to end of study between treatment groups.
The primary endpoint was the change in PCWP over the course of the 24 week study at both rest and peak exercise intensity. The likelihood ratio test examining the statistical significance of the randomized drug was statistically significant (p<0.001) indicating the profiles of changes in PCWP were different between groups.
The secondary endpoint of change in right atrial pressure at rest and peak exercise by likelihood ratio was statistically significant (p<.001).
The secondary endpoint of change in mean pulmonary artery at rest and peak exercise by likelihood was statistically significant (p<.001).
Values represent mean (standard deviation) unless otherwise specified. Abbreviations: PCWP – pulmonary capillary wedge pressure; RA – right atrial; PA – pulmonary arterial