RecentRCT

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Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis

N Engl J Med, 2025 · Phase 3 multicenter double-blind randomized placebo-controlled trial (n=320), stopped early after loss of clinical equipoise

Clinical question

Does add-on sotatercept reduce clinical worsening in intermediate/high-risk PAH diagnosed within the prior year?

Population: Adults with WHO functional class II-III PAH diagnosed <1 year earlier, at intermediate/high risk, receiving double or triple background therapy
Intervention: Sotatercept added to background therapy
Comparator: Placebo added to background therapy
Primary outcome: Time to first clinical-worsening event
Result: Clinical worsening occurred in 10.6% with sotatercept versus 36.9% with placebo (HR 0.24; 95% CI 0.14 to 0.41; P<0.001). (HR 0.24 (95% CI 0.14-0.41), P<0.001)

What the trial found

Adding sotatercept within the first year after PAH diagnosis reduced clinical-worsening events compared with placebo.

Current guideline position

Apply through contemporary PAH specialty recommendations and regulatory labeling; acute ICU RV-crisis management remains physiology- and trigger-driven.

Clinical interpretation

Extends sotatercept evidence earlier in the PAH disease course, but the trial stopped early after prior positive sotatercept results caused loss of equipoise.

Limitations

Stopped early because of loss of clinical equipoise after prior positive trials
The primary endpoint was a composite clinical-worsening outcome

Clinical Context & Relevant Topics (1)

Disease Reference

Pulmonary Hypertension & Acute Decompensation

Hemodynamic classification, right ventricular afterload reduction, selective pulmonary vasodilation, and pulmonary hypertensive crisis management.

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