HI-PEITHO: A LANDMARK Trial
HI-PEITHO is the first large-scale global randomized controlled trial (N=544) powered to determine whether combining EKOS™ catheter-based ultrasound-assisted thrombolysis (USCDT) with anticoagulation (AC) improves outcomes versus the current standard of care - AC alone, in acute intermediate-risk pulmonary embolism (PE).
HI-PEITHO delivers Level-1 evidence to address the critical gaps in PE care:
- Primary endpoint
- Enrollment
- Treatment protocol
- Trial collaboration
7 day composite of:
- PE-related mortality
- Cardiorespiratory decompensation or collapse
- Symptomatic PE recurrence
9
Countries
59
Enrollment Sites
544
Patients
Eligibility criteria:
Intermediate-risk PE with elevated risk of early death or hemodynamic collapse.
- Infusion time: 7 hours
- Unilateral 9mg ƚPA (2mg bolus + 1mg/hr)
- Bilateral: 18mg ƚPA (2mg bolus + 1mg/hr)
- Standardized anticoagulation
Trial Collaborators
HI-PEITHO is a joint research study led by Boston Scientific, in partnership with The PERT Consortium and University Medical Center Mainz, to establish advance therapy with EKOS as a first line treatment for intermediate-risk PE patients.
Principal investigators
Professor Stavros Konstantinides, MD
Internal Medicine, Cardiology
University Medical Center Mainz
Kenneth Rosenfield, MD
Interventional Cardiologist
Massachusetts General Hospital
EKOS demonstrated superiority to AC alone for patients with intermediate-risk PE
Trial design
544 patients
Across 59 hospitals
Targeted risk group
Intermediate-risk PE
Meaningful outcomes
Real clinical data
Trial endpoints & outcomes
Primary endpoint
EKOS demonstrated superiority to AC alone, resulting in a significantly lower rate of the primary composite endpoint (4.0% vs. 10.3%; p=0.005).
Composite of PE-related mortality, cardiorespiratory decompensation or collapse, and symptomatic PE recurrence at 7 days
Primary endpoint components
64% reduction in cardiorespiratory decompensation or collapse with EKOS
Safety outcomes
There was no significant difference in major bleeding between treatment arms and zero ICH events.
Major bleeding at 30 days
ISTH*
4.1%
EKOS
n=271
3.0%
AC Alone
n=271
0
ICH Events
In either study arm
p=0.64
*ISTH: International Society on Thrombosis and Haemostasis
Hospital length of stay
Total hospital length of stay was significantly shorter for patients treated with EKOS.
Hospital total length of stay
Days
NEWS score
HI-PEITHO is the first PE randomized controlled trial to include NEWS in the trial protocol.
The National Early Warning Score (NEWS)2,3 is a standardized and easy-to-use tool that determines the degree of illness and mortality risk of a patient and can be used to prompt critical care intervention.
NEWS provides a scoring system for physiological measurements that are routinely recorded at a patient’s bedside. A score ranging from 0-3 is allocated to each parameter, with higher scores indicating the parameter is further from the normal range. The scores for each parameter are then added together to determine the NEWS Score.
Trial bibliography
HI-PEITHO was presented as the first Late-Breaking Clinical Trial (LBCT) session at The American College of Cardiology’s Annual Scientific Session & Expo (ACC.26) with a simultaneous publication in The New England Journal of Medicine, on March 28, 2026.
The primary conclusion demonstrated that, in patients with acute, intermediate-risk PE, ultrasound‑facilitated, catheter‑directed fibrinolysis combined with anticoagulation reduced the risk of the composite endpoint—PE‑related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of PE within seven days—compared with anticoagulation alone.
Principal Investigators: Ken Rosenfeld, M.D., Section Head, Vascular Medecine and Intervention, Division of Cardiology, Mass General Hospital, Boston, Massachussets ; Stavros Konstantinidis, M.D. Ph.D. FESC, FRCP (Glasgow), Professor, Clinical Trials, and Medical Director (CTH), Johannes Gutenberg University, Mainz.
A complete list of the HI-PEITHO investigators is provided in the Supplementary Appendix, available at NEJM.org.
References:
1. Rosenfield K, Klok FA, Piazza G, et al. Ultrasound‑facilitated, catheter‑directed fibrinolysis for acute pulmonary embolism. N Engl J Med. 2026. doi:10.1056/NEJMoa2516567
2. Royal College of Physicians. National Early Warning Score (NEWS): Standardising the assessment of acute-illness severity in the NHS. Report of a working party. London: RCP, 2012
3. National Institute for Health and Care Excellence. (2019). National early warning score systems that alert to deteriorating adult patients in hospital (MIB205) Available from: Overview | National Early Warning Score systems that alert to deteriorating adult patients in hospital | Advice | NICE
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