Pulmonary vascular disease & thromboembolism
Ralinepag for the treatment of pulmonary arterial hypertension (ADVANCE OUTCOMES): a randomised, double-blind, placebo-controlled phase 3 study
Primary result · First clinical worsening eventResult — go to the resultHazard ratio 0.45 95% CI 0.33–0.62Authors' conclusion
In patients with PAH receiving contemporary background therapy, ralinepag significantly reduced the risk of first clinical worsening compared with placebo, but was associated with more adverse-event-related treatment discontinuations.
Study context
- Population
- Adults with pulmonary arterial hypertension (PAH) (2022 ESC/ERS criteria) on contemporary background therapy687 analysed
- Participants
- 728 adults
- Comparison
- Ralinepag vs placebo
- Ralinepagn = 350
- Placebon = 337reference
- Primary endpoint
- Time to first clinical worsening event:
- Death from any cause
- Hospital admission for worsening PAH or right HF
- Initiation of parenteral or inhaled prostacyclin-pathway therapy
- Disease progression
- Unsatisfactory long-term clinical response
Methodological detailsdouble-blind, placebo-controlled, event-driven, phase 3, Median follow-up 85.0 weeks (IQR 27.6-160.9) with ralinepag and 78.4 weeks (34.6-137) with placebo
- Double-blind
- Placebo-controlled
- Event-driven
- Phase 3
- Median follow-up 85.0 weeks (IQR 27.6-160.9) with ralinepag and 78.4 weeks (34.6-137) with placebo
Primary result
First clinical worsening event
Hazard ratio
0.45
95% CI 0.33–0.62
P < 0.0001
Events by treatment group
Ralinepag vs Placebo
HR 0.45 (95% CI 0.33–0.62); P < 0.0001
As reported in the abstract
Further findings
Components of the composite outcome
- Largest numerical between-group differences for disease progression, initiation of parenteral or inhaled prostacyclin-pathway therapy, and unsatisfactory long-term clinical response
Safety
Treatment discontinuation primarily due to adverse event
Serious adverse events
Adverse events leading to death
Original publication
Ralinepag for the treatment of pulmonary arterial hypertension (ADVANCE OUTCOMES): a randomised, double-blind, placebo-controlled phase 3 study. Lancet. Published 28 July 2026. doi:10.
Summarised from the published abstract; every number is checked against it