In patients with acute intermediate-risk pulmonary embolism and additional signs of cardiorespiratory distress, ultrasound-facilitated catheter-directed fibrinolysis plus anticoagulation reduced early PE-related clinical deterioration compared with anticoagulation alone, without a statistically significant increase in major bleeding.
Study design
- Multinational, randomized, open-label trial with blinded outcome adjudication
- Adaptive design
- 59 sites in the United States and Europe
- 2021 to 2025
- N = 544
Population
- Acute intermediate-risk pulmonary embolism
- RV/LV end-diastolic diameter ratio ≥1.0
- Elevated troponin
- At least 2 signs of cardiorespiratory distress
- SBP ≤110 mmHg, HR ≥100 bpm, or RR >20/min
- Mean age 58.2
- 42.6% women
Interventions
- USCDT + anticoagulation: 273
- Anticoagulation alone: 271
- USCDT used ultrasound-facilitated catheter-directed alteplase
- Most patients received heparin-based anticoagulation
Primary outcome
- Composite: PE-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrent PE
- Assessed within 7 days
- 4.0% with USCDT + anticoagulation vs 10.3% with anticoagulation alone
- RR 0.39; 95% CI 0.20-0.77
- P = 0.005
- Superiority met
USCDT + AC vs AC alone
Primary composite endpoint at 7 days
4.0% vs 10.3% | RR 0.39
Primary composite: PE-related death, cardiorespiratory decompensation/collapse, or symptomatic recurrent PE within 7 days.
Secondary outcomes
- Cardiorespiratory decompensation/collapse: 3.7% vs 10.3%
- PE-related death at 7 days: 1.1% vs 0.4%
- Symptomatic recurrent PE: 0.4% vs 0.4%
- Rescue therapy: 2.9% vs 9.2%
- All-cause mortality at 30 days: 1.8% vs 1.1%
- No intracranial hemorrhage in either group
Safety
- Major bleeding at 7 days: 4.1% vs 2.2%
- Major bleeding at 30 days: 4.1% vs 3.0%
- No statistically significant difference in major bleeding
- No intracranial bleeding
- Serious adverse events were similar between groups
Interpretation
- USCDT reduced early clinical deterioration in a carefully selected, higher-risk intermediate PE population
- Benefit was mainly driven by less cardiorespiratory decompensation/collapse
- No mortality benefit was shown
- Strict selection matters; these results should not be generalized to all intermediate-risk PE
- Bleeding was numerically higher with USCDT, but not statistically significant
Rosenfield, K., et al. (2026). Ultrasound-facilitated, catheter-directed fibrinolysis for acute pulmonary embolism. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2516567