Effect of macitentan on haemodynamics in patients with pulmonary arterial hypertension: results from the long-term, randomised, placebo-controlled SERAPHIN trial
Bibliographic record
Abstract
Purpose: Macitentan, a novel dual endothelin receptor antagonist (ERA), significantly reduced morbidity and mortality in pulmonary arterial hypertension (PAH) patients in the Phase III SERAPHIN trial (NCT00660179). The effect of macitentan on haemodynamics assessed in a substudy is reported. Methods: 742 PAH patients were randomised to placebo, macitentan 3mg or 10mg, once daily. Stable background PAH therapy, except injectable prostanoids and other ERAs, were allowed. At selected centres patients underwent right heart catheterisation at randomisation and Month 6. Changes from baseline to Month 6 for mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI) and mixed venous oxygen saturation (SvO2) were calculated for all patients and stratified in an exploratory analysis for background PAH therapy and baseline WHO FC I/II vs III/IV. Median treatment effects (95% CL) between placebo and macitentan are reported. Results: 187 patients participated in the substudy (51% were treatment-naïve and 56% in WHO FC III/IV). Baseline median values for all patients on placebo (n=68), macitentan 3mg (n=62) and 10mg (n=57) were: mRAP 7.0, 8.0, 7.0 mmHg; mPAP 52.0, 54.0, 52.3 mmHg; PVR 800, 785, 789 dyn·sec/cm5; CI 2.49, 2.23, 2.47 L/min/m2; and SvO2 66.0, 64.5, 66.5%. Overall, haemodynamic parameters improved at Month 6 with macitentan and worsened with placebo. Table shows beneficial treatment effects with macitentan that were statistically significant (p<0.05) for PVR and CI for both subgroups (except PVR macitentan 3mg treatment-naïve). Table 1. Treatment effect on PVR and CI Median (95% CL) placebo-corrected change from baseline and Wilcoxon test P-values; *based on the log of Month 6/baseline values. Conclusions: Macitentan significantly improved cardio-pulmonary haemodynamics in PAH patients. Improvements in PVR and CI were consistent irrespective of background PAH therapy and baseline WHO FC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".