EKOS has announced the publication of results of the SEATTLE II trial in the JACC: Cardiovascular Interventions. The study concluded that treatment with ultrasound-facilitated catheter-directed low-dose thrombolysis for acute pulmonary embolism improves right heart function, reduces blood clot size, and decreases pulmonary hypertension in patients with intermediate to high risk pulmonary embolism. Importantly, no patient experienced intracranial haemorrhage, a serious adverse experience related to full-dose thrombolysis treatment.
The SEATTLE II study was a prospective, single-arm, multicentre trial designed to evaluate the safety and effectiveness of ultrasound-facilitated catheter-directed low-dose thrombolysis, using the EKOS EkoSonic endovascular system. One-hundred and fifty patients diagnosed as acute massive (n=31) or submassive (n=119) pulmonary embolism were enrolled. Patients received a low dose (24mg) tissue plasminogen activator (thrombolytic) for 24 hours with a unilateral catheter or for 12 hours with bilateral catheters. The size of the right heart measured as right ventricle/left ventricle ratio significantly decreased from 1.55 to 1.13 (p<0.0001) by 48 hours after start of treatment.
For patients with severe pulmonary embolism, the mortality rate is nearly one third. In the SEATTLE II study 31 patients presented to the emergency room with massive pulmonary embolism, syncope and hypotension. All 31 survived the 30-day follow up period. Of 150 patients in the study, one death was directly attributed to pulmonary embolism.
There were no intracranial haemorrhages and no fatal bleeding events. Major bleeds occurred in 15 patients and were comprised of one severe bleed and 16 moderate bleeds. Six of the major bleeds occurred in patients with co-morbidities known to be associated with an increased risk of bleeding during thrombolytic therapy.
“The SEATTLE II findings establish a new rationale for considering ultrasound-facilitated catheter-directed low-dose thrombolysis in both massive and submassive pulmonary embolism,” said Gregory Piazza, assistant professor of medicine, Harvard Medical School, staff physician, Cardiovascular Division, Brigham and Woman’s Hospital (Boston, USA), and principal investigator for SEATTLE II. “Without any intracranial haemorrhage and using a much reduced lytic dose, a substantial and clinically meaningful reduction of the right ventricle/left ventricle ratio was achieved.”
“The SEATTLE II and ULTIMA trials add to the body of evidence showing treatment with the EkoSonic endovascular system improves the standard of care for patients with acute pulmonary embolism,” said Matt Stupfel, general manager of EKOS Corporation. “The only endovascular device cleared by the Food and Drug Administration for the treatment of pulmonary embolism, EkoSonic represents a potential game-changer in the treatment of high-risk pulmonary embolism patients. EKOS ultrasonic waves greatly accelerate lytic dispersion by driving the drug deeper into the clot and unwinding fibrin to expose plasminogen receptor sites.”
The ULTIMA trial, published January 2014 in Circulation, demonstrated that EKOS treatment was clinically superior to anticoagulation with heparin alone in reversing right ventricular enlargement at 24 hours, without an increase in bleeding complications. Building on the success of SEATTLE II and ULTIMA for treatment of pulmonary embolism, EKOS is launching the next study, OPTALYSE PE, to better understand the optimal dose of thrombolytic and duration of its treatment.