Table 1.
Summary of the main results from the SERAPHIN trial in the overall study population
| Variable | Macitentan 10 mg (N = 242) | Placebo (N = 250) | Treatment effect (Macitentan 10 mg vs. Placebo) | |
|---|---|---|---|---|
| Morbidity event or death as the first eventa [5] | 76 (31.4) | 116 (46.4) | HR 0.55 (97.5% CL 0.39–0.76) | p < 0.001 |
| PAH-related death or hospitalizationa [5] | 50 (20.7) | 84 (33.6) | HR 0.50 (97.5% CL 0.34–0.75) | p < 0.001 |
| PAH-related hospitalizationa,b [20] | 46 (19.0) | 80 (32.0) | HR 0.48 (95% CL 0.34–0.70) | p < 0.0001 |
| Change in 6MWD from BL to month 6, m [5] | 12.5 ± 83.5 | − 9.4 ± 100.6 | LSMD 22.8 (97.5% CL 4.0–41.5) | p = 0.008 |
| Patients improving in WHO FC from BL to month 6 [5] | 54 (22) | 32 (13) | OR 1.95 (95% CL 1.21–3.14) | p = 0.006 |
| HRQoLc [34]d | ||||
| Change from BL to month 6 in SF-36 PCS scores | 2.3 ± 7.8 | − 0.7 ± 8.7 | Mean placebo-corrected change from BL 3.0 (97.5% CL 1.3–4.7) | – |
| Change from BL to month 6 in SF-36 MCS scores | 1.3 ± 11.3 | − 2.1 ± 12.6 | Mean placebo-corrected change from BL 3.4 (97.5% CL 0.9–5.9) | – |
| Change in cardiopulmonary hemodynamic parameters and NT-proBNPe,f [16] | ||||
| Cardiac index, l/min/m2 | 0.30 ± 0.85 | − 0.33 ± 0.65 | 0.63 (95% CL 0.33, 0.93) | p < 0.05 |
| PVR, % | 71.3 (62.4, 81.4) | 115.8 (104.7, 128.1) | − 38.5 (95% CL − 47.8, − 27.5) | p < 0.05 |
| mPAP, mmHg | − 5.3 ± 11.4 | 1.0 ± 7.4 | − 6.4 (95% CL − 10.2, − 2.5) | p < 0.05 |
| NT-proBNP, fmol/ml | − 109 ± 552 | 194 ± 575 | − 303 (95% CL − 533, − 73) | p < 0.05 |
Data are presented as n (%) or mean ± SD
6MWD 6-minute walk distance, BL baseline, CL confidence limit, HR hazard ratio, HRQoL health-related quality of life, LSMD least-squares mean difference, MCS mental component summary, mPAP mean pulmonary arterial pressure, NT-proBNP N-terminal pro-brain natriuretic peptide, OR odds ratio, PAH pulmonary arterial hypertension, PCS physical component summary, PVR pulmonary vascular resistance, SD standard deviation, SF-36 36-Item Short-Form survey, WHO FC World Health Organization functional class
aEndpoints evaluated up to the end of the double-blind treatment period (median duration of treatment, 115 weeks)
bPost hoc analysis
cA higher SF-36 score denotes better HRQoL (scale, 0–100). Ten patients in the placebo group and eight patients in the macitentan 10 mg group were excluded as they were either aged < 14 years or did not have a complete HRQoL assessment at baseline (i.e., they did not have baseline data for all eight health domains, a PCS score and an MCS score). In addition, one patient in the placebo arm did not receive any treatment and was therefore excluded from the analysis
dActelion unpublished data
eFor the change from BL to month 6, PVR data are the geometric mean of month 6/baseline (%) (95% CL), data for all other hemodynamic variables are mean ± SD. For the treatment effect, PVR data are expressed as a percent change (%) between macitentan and placebo: (ratio of geometric means − 1) × 100; data for all other variables are the placebo-corrected mean ± SD
fShown only for the patients in the hemodynamic sub-study with non-missing values for change from BL to month 6, as follows: for cardiac index n = 48 for macitentan, n = 50 for placebo; for PVR n = 48 for macitentan, n = 50 for placebo; for mPAP n = 49 for macitentan, n = 50 for placebo; for NT-proBNP n = 46 for macitentan, n = 49 for placebo