PULSAR (low-dose sotatercept)
Trial question
What is the role of low-dose sotatercept in patients with pulmonary arterial hypertension?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
86.0% female
14.0% male
N = 64
64 patients (55 female, 9 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=32 low-dose sotatercept (subcutaneous dose of 0.3 mg/kg every 3 weeks for 24 weeks).
N=32 placebo (matching placebo every 3 weeks for 24 weeks).
Primary outcome
Reduction in pulmonary vascular resistance at week 24
162.2
16.4
162.2 dyn•s/...
121.6 dyn•s/...
81.1 dyn•s/...
40.5 dyn•s/...
0.0 dyn•s/...
Low-dose
sotatercept
Placebo
Significant
increase ▲
Significantly greater reduction in pulmonary vascular resistance at week 24 (162.2 dyn•s/cm⁵ vs. 16.4 dyn•s/cm⁵; AD 145.8 dyn•s/cm⁵, 95% CI 50.6 to 241).
Secondary outcomes
Significantly greater improvement in 6-minute walk distance at week 24 (58.1 m vs. 28.7 m; AD 29.4 m, 95% CI 3.8 to 55).
Significantly greater reduction in NT-proBNP level at week 24 (621.1 pg/mL vs. -310.4 pg/mL; AD 931.5 pg/mL, 95% CI 509.7 to 1353.2).
No significant difference in reduction in systolic excursion from the tricuspid annular plane at week 24 (0 vs. 0).
Safety outcomes
No significant difference in any adverse event.
Significant difference in thrombocytopenia (6% vs. 0%).
Conclusion
In adult patients who were receiving background therapy for pulmonary arterial hypertension, low-dose sotatercept was superior to placebo with respect to reduction in pulmonary vascular resistance 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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