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Vascular Surgery / Venous Thromboembolism / Pulmonary Embolism / Clinical Data

 

EKOS Clinical Evidence

 

 

The EKOS™ Endovascular System is the most studied device in the pulmonary embolism space. Since 2014, several major studies have demonstrated clinically significant results in quality of life scores1, mortality2, and long-term safety and efficacy1,3,4 for acute, massive (high risk) and submassive (intermediate risk) PE.

Today, more research is underway, both to confirm established clinical results (KNOCOUT Registry), as well as to address critical gaps in clinical evidence when comparing the clinical benefit of intervention with EKOS™ vs anticoagulation alone (Hi-PEITHO ).

EKOS clinical results

  • EKOS brings 23-26% reduction to the RV/LV ratio – without an increase in bleeding1, 3, 4
  • It allows for lower lytic doses – up to 88-92% less than for standard systemic treatment – and shorter delivery duration of the thrombolytic agent5,1
  • It enables shorter average length of hospital stay (3.2 days) than for patients being treated with anticoagulation alone (6.7 days)6

The Studies

ULTIMA, 2014

The ULTIMA trial was the first randomised controlled trial (RCT) to examine ultrasound-accelerated thrombolysis vs anticoagulation.
Scope: 59 patients in Switzerland and Germany
Results: The trial showed that a fixed-dose EKOS regimen was superior to anticoagulation alone in improving right ventricular dysfunction, with a 23% reduction in RV/LV ratio at 24 hours3 – without an increase in bleeding complications.
Read about the ULTIMA trial >

 

Nykamp and Laurich, 2015

Scope: 45 patients
Results: The key outcome of this study was that it showed a reduction in average length of hospital stay for patients treated with EKOS (3.2 days) vs those treated only with anticoagulation (6.7 days)6
Read about the Nykamp and Laurich study >

 

SEATTLE II, 2015

The SEATTLE II trial, a larger single arm prospective study, consolidated the RV/LV results.
Scope: 150 patients
Results: It showed a 25% decrease in RV/LV ratio over 48 hours via CTPA (pre/post CTPA)4.
More results from the SEATTLE II trial >

 

OPTALYSE, 2018

Many participating physicians in the SEATTLE study saw patients improve in a matter of hours, which led them to ask: What would be the consequences if they stopped earlier than with the study’s 12hrs/24mg tPA treatment protocol? This led to the OPTALYSE trial.
Scope: Four groups of about 25 patients randomised to a specific time and dose. The shortest duration was 2 hours and 4mgs of tPA, while the longest was 6hrs and 24mgs. (To compare, the SEATTLE II study was at 12hrs/24mg tPA.)
Results: At 48hrs all groups improved significantly in RV/LV ratio1. Other cardiac parameters improved most in the 6hr/12mg group. Patients had follow-up until 1y; results were also published.
OPTALYSE also demonstrated a 23-26% decrease in the RV/LV ration in 48 hrs3, as well as a bleeding rate of 3%.1
Learn more about the OPTALYSE trial >

 

Confirming results with the KNOCOUT PE Registry

Results observed in the OPTALYSE trial are now being confirmed with the KNOCOUT PE registry, which presented 3-month data for the prospective cohort of 489 patients in 2021.
Scope: A prospective cohort of 489 patients across 83 international sites in the US and Europe; and a retrospective cohort of 991 patients
Purpose: KNOCOUT was established to measure institutional adoption of a lower dose and lower-duration thrombolysis protocol for the EKOS system. It adds to the growing evidence that EKOS is effective at treating intermediate risk and high risk PE with lower lytic doses and shorter infusion durations compared to other thrombolytic therapies.
Get full details on the KNOCOUT study >

Comparing EKOS + anticoagulation vs anticoagulation alone: the HI-PEITHO study

HI-PEITHO is a randomised control trial designed to compare low dose EKOS™ ultrasound-accelerated thrombolysis in combination with anticoagulation vs anticoagulation alone. This study, which has begun enrolling patients in Europe and the US in December 2021, will also compare interventional therapy in combination with anticoagulation vs anticoagulation alone for the treatment of intermediate high-risk pulmonary embolism.

Scope: The randomised HI-PEITHO trial will enroll up to 544 patients with confirmed acute, intermediate-high-risk PE at as many as 65 sites in the U.S. and Europe.
Purpose: The trial, which will follow patients for one year, will assess whether treatment with the EKOS system in combination with anticoagulation is associated with a significant reduction in adverse events compared to anticoagulation alone, within seven days of randomisation.
Endpoints: The composite primary endpoint is defined as PE-related mortality, cardiorespiratory decompensation or collapse and non-fatal symptomatic and objectively confirmed recurrence of PE. (View HI-PEITHO study details).

 

The clinical studies: a bibliography

2014 - ULTIMA: Randomised, Controlled Trial of Ultrasound-Assisted Catheter-Directed Thrombolysis for Acute Intermediate-Risk Pulmonary Embolism
Nils Kucher, MD et al. Circulation 2014; 129: 479-486
[https://pubmed.ncbi.nlm.nih.gov/24226805/]
SUMMARY / ARTICLE

2015 - SEATTLE II: A Prospective, Single-Arm, Multicentre Trial of Ultrasound-Facilitated, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism
G. Piazza MD, MS et al, JACC Cardiovasc Interv. 2015 Aug 24; 8(10): 1382-92
[https://pubmed.ncbi.nlm.nih.gov/26315743/]
SUMMARY / ARTICLE

2015 – Nykamp and Laurich study: Safety and Efficacy of Ultrasound-Accelerated Catheter-Directed Lytic Therapy in Acute Pulmonary Embolism With and Without Haemodynamic Instability
Nykamp M et al. J Vasc Surg: Venous and Lymphatic Disorders 2015: 3(5) 251-7
[https://www.jvsvenous.org/article/S2213-333X(15)00053-0/fulltext]
SUMMARY / ARTICLE

2018 – OPTALYZE PE: Optimum Duration and Dose of tPA with the Acoustic Pulse Thrombolysis Procedure for Submassive Pulmonary Embolism: OPTALYSE PE
Tapson, Victor, et al., “A Randomised Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial.” JACC: Cardiovascular Interventions Jul 2018, 11 (14) 1401-10
[https://pubmed.ncbi.nlm.nih.gov/30025734/]
SUMMARY / ARTICLE

2020 – OPTALYSE PE: G. Piazza MD, MS et al., “One-Year Echocardiographic, Functional, and Quality of Life Outcomes After Ultrasound-Facilitated Catheter-Based Fibrinolysis for Pulmonary Embolism.” Cardiovascular Interventions Aug 2020, 13 (08), :e009012. doi: 10.1161/CIRCINTERVENTIONS.120.009012. Epub 2020 Aug 6. PMID: 32757658; PMCID: PMC7434215.
[https://pubmed.ncbi.nlm.nih.gov/32757658
SUMMARY / ARTICLE

2021 – KNOCOUT: International EkoSonic Registry of the Treatment and Clinical Outcomes of Patients with Pulmonary Embolism Prospective Cohort 3-month Data Release
Principal Investigators: Samuel Z. Goldhaber, MD; Stavros V. Konstantinides, MD PhD; Nicolas Meneveau, MD PhD; Victor F. Tapson, MD; Keith M. Sterling, MD; Nils Kucher, MD; Robert Maholic, DO; Mahir Elder, MD; Gregory Piazza, MD; Andrew SP Sharp, MD; Noah Jones, MD -
SUMMARY

Underway – HI-PEITHO: The HI-PEITHO study has been designed to address a critical gap in clinical evidence in PE by comparing the clinical benefit of intervention with EKOS vs. the current standard of care – anticoagulation. Hear from the Principal Investigators / Get Study details
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

 

 

 

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Page last updated: May 2022
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