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The following is a summary of “Safety and efficacy of rodatristat ethyl for the treatment of pulmonary arterial hypertension (ELEVATE-2): a dose-ranging, randomised, multicentre, phase 2b trial,” published in the November 2024 issue of Pulmonology by Sitbon et al. 

Researchers conducted a retrospective study to evaluate the association between serotonin levels and pulmonary arterial hypertension severity and clinical outcomes.  

They performed a Phase 2b, randomized, double-blind clinical trial (ELEVATE-2) to investigate rodatristat ethyl for pulmonary arterial hypertension (PAH) and enrolled 108 patients across 16 countries in Europe and North America. Eligible participants were 18 or older with WHO functional class II or III PAH and were on stable PAH medication for at least 12 weeks. Patients were randomly assigned to receive a placebo, 300mg rodatristat ethyl once daily with placebo, or 300mg rodatristat ethyl twice daily for 24 weeks. Neither patients nor researchers knew treatment allocation (double-blind). The primary outcome was a change in pulmonary vascular resistance (PVR) after 24 weeks.  

The results showed that 108 participants enrolled between March 18, 2021, and December 13, 2022, were randomly assigned to placebo (n=36), rodatristat ethyl 300 mg (n=36), or rodatristat ethyl 600 mg (n=36) twice daily. Most participants were female (85%, n=85), with a mean age of 52.8 years (SD 14.7). The primary endpoint, PVR, favored the placebo, with a 5.8% (SE 18.1) decrease in the placebo group, a 63.1% (18.5) increase in the rodatristat ethyl 300 mg group, and a 64.2% (18.0) increase in the rodatristat ethyl 600 mg group. Treatment-emergent adverse events (TEAEs) occurred in 81% of the placebo group, 92% of the rodatristat ethyl 300 mg group, and 100% of the rodatristat ethyl 600 mg group, while TEAEs leading to study discontinuation occurred in 8% of the placebo group, 11% of the rodatristat ethyl 300 mg group, and 11% of the rodatristat ethyl 600 mg group with 1 death occurred in the rodatristat ethyl 300 mg group.   

Investigators concluded that reducing peripheral serotonin concentrations with rodatristat ethyl negatively impacted pulmonary haemodynamics and cardiac function in patients with PAH.  

Source: thelancet.com/journals/lanres/article/PIIS2213-2600(24)00226-1/abstract