Results for 6MWD, TRV, NT-proBNP, and BDS by time point
| . | Sildenafil . | Placebo . | P* . | ||||
|---|---|---|---|---|---|---|---|
| N . | Mean (SD) . | Median (min, max) . | N . | Mean ± SD . | Median (min, max) . | ||
| Baseline | 37 | 381 ± 75 | 383 (198, 494) | 37 | 386 ± 75 | 390 (175, 492) | .76 |
| Week 6 | 25 | 372 ± 89 | 368 (176, 504) | 24 | 428 ± 81 | 440 (240, 530) | .16 |
| Week 10 | 19 | 374 ± 86 | 366 (180, 485) | 16 | 423 ± 82 | 433 (248, 539) | .16 |
| Week 16 | 15 | 364 ± 101 | 363 (190, 515) | 14 | 410 ± 105 | 431 (205, 564) | .34 |
| Imputed last visit | 37 | 361 ± 103 | 388 (176, 15) | 37 | 375 ± 122 | 408 (0, 564) | .73 |
| Primary analysis: ANCOVA model (LS mean SE) | −16 (20) | −7 (20) | |||||
| Difference sildenafil − placebo (95% CI) | −9 (−56, 38) | .70 | |||||
| Tricuspid regurgitant jet velocity, m/s | |||||||
| Baseline | 37 | 3.1 ± 0.5 | 2.8 (2.4, 4.3) | 37 | 3.0 ± 0.3 | 2.8 (2.7, 3.7) | .15 |
| Week 6 | 25 | 3.2 ± 0.7 | 2.9 (2.5, 4.7) | 24 | 2.9 ± 0.3 | 2.8 (2.6, 3.6) | .06 |
| Week 16 | 15 | 2.9 ± 0.5 | 2.7 (2.3, 4.1) | 14 | 2.9 ± 0.3 | 2.8 (2.5, 3.4) | .45 |
| Mixed effects regression (LS mean SE) | 3.00 (0.046) | 2.96 (0.045) | |||||
| Difference sildenafil − placebo (95% CI) | 0.04 (−0.08, 0.15) | .50† | |||||
| Brain natriuretic peptide (log10), pg/L | |||||||
| Baseline | 35 | 2.3 ± 0.6 | 2.3 (0.6, 3.6) | 35 | 2.0 ± 0.6 | 1.9 (0.6, 3.2) | .03 |
| Week 6 | 22 | 2.4 ± 0.4 | 2.4 (1.8, 3.1) | 22 | 2.0 ± 0.7 | 1.8 (0.6, 3.6) | .08 |
| Week 10 | 17 | 2.3 ± 0.5 | 2.2 (1.6, 3.5) | 14 | 2.2 ± 0.6 | 2.1 (1.6, 3.7) | .67 |
| Week 16 | 14 | 2.5 ± 0.7 | 2.4 (1.6, 3.7) | 12 | 2.3 ± 0.6 | 2.1 (1.8, 3.8) | .41 |
| Mixed effects regression (LS mean SE) | 2.40 (0.087) | 2.30 (0.093) | |||||
| Difference sildenafil − placebo (95% CI) | 0.11(−0.15, 0.36) | .41† | |||||
| BDS | |||||||
| Baseline | 37 | 2.5 ± 2.1 | 2.0 (0.0, 7.0) | 37 | 2.1 ± 2.0 | 2.0 (0.0, 9.0) | .28 |
| Week 6 | 25 | 3.4 ± 2.3 | 3.0 (0.0, 8.0) | 24 | 1.8 ± 1.3 | 2.0 (0.0, 4.0) | .003 |
| Week 10 | 19 | 2.7 ± 2.0 | 3.0 (0.0, 8.0) | 16 | 2.7 ± 1.7 | 3.0 (0.0, 6.0) | .67 |
| Week 16 | 15 | 2.0 ± 1.6 | 2.0 (0.0, 5.0) | 14 | 2.8 ± 2.4 | 2.5 (0.0, 7.0) | .51 |
| Mixed effects regression (LS mean SE) | 2.24 (0.396) | 2.62 (0.408 | |||||
| Difference sildenafil − placebo (95% CI) | 0.37 (−1.51, 0.77) | ||||||
| . | Sildenafil . | Placebo . | P* . | ||||
|---|---|---|---|---|---|---|---|
| N . | Mean (SD) . | Median (min, max) . | N . | Mean ± SD . | Median (min, max) . | ||
| Baseline | 37 | 381 ± 75 | 383 (198, 494) | 37 | 386 ± 75 | 390 (175, 492) | .76 |
| Week 6 | 25 | 372 ± 89 | 368 (176, 504) | 24 | 428 ± 81 | 440 (240, 530) | .16 |
| Week 10 | 19 | 374 ± 86 | 366 (180, 485) | 16 | 423 ± 82 | 433 (248, 539) | .16 |
| Week 16 | 15 | 364 ± 101 | 363 (190, 515) | 14 | 410 ± 105 | 431 (205, 564) | .34 |
| Imputed last visit | 37 | 361 ± 103 | 388 (176, 15) | 37 | 375 ± 122 | 408 (0, 564) | .73 |
| Primary analysis: ANCOVA model (LS mean SE) | −16 (20) | −7 (20) | |||||
| Difference sildenafil − placebo (95% CI) | −9 (−56, 38) | .70 | |||||
| Tricuspid regurgitant jet velocity, m/s | |||||||
| Baseline | 37 | 3.1 ± 0.5 | 2.8 (2.4, 4.3) | 37 | 3.0 ± 0.3 | 2.8 (2.7, 3.7) | .15 |
| Week 6 | 25 | 3.2 ± 0.7 | 2.9 (2.5, 4.7) | 24 | 2.9 ± 0.3 | 2.8 (2.6, 3.6) | .06 |
| Week 16 | 15 | 2.9 ± 0.5 | 2.7 (2.3, 4.1) | 14 | 2.9 ± 0.3 | 2.8 (2.5, 3.4) | .45 |
| Mixed effects regression (LS mean SE) | 3.00 (0.046) | 2.96 (0.045) | |||||
| Difference sildenafil − placebo (95% CI) | 0.04 (−0.08, 0.15) | .50† | |||||
| Brain natriuretic peptide (log10), pg/L | |||||||
| Baseline | 35 | 2.3 ± 0.6 | 2.3 (0.6, 3.6) | 35 | 2.0 ± 0.6 | 1.9 (0.6, 3.2) | .03 |
| Week 6 | 22 | 2.4 ± 0.4 | 2.4 (1.8, 3.1) | 22 | 2.0 ± 0.7 | 1.8 (0.6, 3.6) | .08 |
| Week 10 | 17 | 2.3 ± 0.5 | 2.2 (1.6, 3.5) | 14 | 2.2 ± 0.6 | 2.1 (1.6, 3.7) | .67 |
| Week 16 | 14 | 2.5 ± 0.7 | 2.4 (1.6, 3.7) | 12 | 2.3 ± 0.6 | 2.1 (1.8, 3.8) | .41 |
| Mixed effects regression (LS mean SE) | 2.40 (0.087) | 2.30 (0.093) | |||||
| Difference sildenafil − placebo (95% CI) | 0.11(−0.15, 0.36) | .41† | |||||
| BDS | |||||||
| Baseline | 37 | 2.5 ± 2.1 | 2.0 (0.0, 7.0) | 37 | 2.1 ± 2.0 | 2.0 (0.0, 9.0) | .28 |
| Week 6 | 25 | 3.4 ± 2.3 | 3.0 (0.0, 8.0) | 24 | 1.8 ± 1.3 | 2.0 (0.0, 4.0) | .003 |
| Week 10 | 19 | 2.7 ± 2.0 | 3.0 (0.0, 8.0) | 16 | 2.7 ± 1.7 | 3.0 (0.0, 6.0) | .67 |
| Week 16 | 15 | 2.0 ± 1.6 | 2.0 (0.0, 5.0) | 14 | 2.8 ± 2.4 | 2.5 (0.0, 7.0) | .51 |
| Mixed effects regression (LS mean SE) | 2.24 (0.396) | 2.62 (0.408 | |||||
| Difference sildenafil − placebo (95% CI) | 0.37 (−1.51, 0.77) | ||||||
Statistics for the 6MWD test were based on an ANCOVA model with treatment as a fixed effect and baseline 6MWD distance, TRV stratum, and study site as covariates. The P value for TRV by time point corresponds to an ANOVA model with treatment by strata as cells testing the hypothesis that the average values do not differ between the 2 treatment groups.
The P values for the repeated measures analyses are based on a linear mixed effects model with treatment, baseline value, time, and study site as fixed effects, and subject as a random effect using all available data from the randomized population, testing the hypotheses of no difference between the treatment groups after 16 weeks of therapy.
LS mean SE indicates least squares mean standard error.