PULSAR (high-dose sotatercept)
Trial question
What is the role of high-dose sotatercept in patients with pulmonary arterial hypertension?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
89.0% female
11.0% male
N = 74
74 patients (66 female, 8 male)
Inclusion criteria: adult patients who were receiving background therapy for pulmonary arterial hypertension
Key exclusion criteria: portopulmonary disease; schistosomiasis; and HIV infection-associated pulmonary arterial hypertension; portal hypertension or chronic liver disease
Interventions
N=42 high-dose sotatercept (subcutaneous dose of 0.7 mg/kg every 3 weeks for 24 weeks)
N=32 placebo (matching placebo every 3 weeks for 24 weeks)
Primary outcome
Pulmonary vascular resistance reduction at week 24
255.9
16.4
255.9 dyn•s/...
191.9 dyn•s/...
128.0 dyn•s/...
64.0 dyn•s/...
0.0 dyn•s/...
High-dose
sotatercept
Placebo
Significant
increase ▲
Significant increase in pulmonary vascular resistance reduction at week 24 (255.9 dyn•s/cm⁵ vs. 16.4 dyn•s/cm⁵; AD 239.5 dyn•s/cm⁵, 95% CI 149.7 to 329.3)
Secondary outcomes
No significant difference in improvement in 6-minute walk distance at week 24 (50.1 m vs. 28.7 m; AD 21.4 m, 95% CI -2.8 to 45.7)
Significant increase in NT-proBNP level reduction at week 24 (340.6 pg/mL vs. -310.4 pg/mL; AD 651 pg/mL, 95% CI 258.7 to 1043.3)
Significant increase in reduction in systolic excursion from the tricuspid annular plane at week 24 (0.1 cm vs. 0 cm; AD 0.1 cm, 95% CI 0.08 to 0.2)
Safety outcomes
No significant difference in any adverse event.
Significant difference in thrombocytopenia (12% vs. 0%).
Conclusion
In adult patients who were receiving background therapy for pulmonary arterial hypertension, high-dose sotatercept was superior to placebo with respect to pulmonary vascular resistance reduction at week 24.
Reference
Marc Humbert, Vallerie McLaughlin, J Simon R Gibbs et al. Sotatercept for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2021 Apr 1;384(13):1204-1215.
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