News From ISET: OPTALYSE PE Long Term Results Reinforce Safety and Efficacy of Shorter, Lower Dose EKOS Therapy For Pulmonary Embolism

BTG plc highlighted OPTALYSE PE one-year trial results, presented at the International Society on Endovascular Therapy (ISET), February 3-7, 2018, in Hollywood, Florida. The findings confirm that bilateral pulmonary embolism (PE) patients treated in as little as 2 hours with a total tissue plasminogen activator (tPA) dose as low as 8 mg continue to show improvements in right ventricular/left ventricular (RV/LV) ratio over the long term with a very low all-cause mortality rate of 2%, an equally low recurrent PE rate of 2%, and continued quality of life improvements — further demonstrating the efficacy and safety of the OPTALYSE PE treatment regimens.

“The long-term follow-up results reinforce that a new interventional standard is being set for PE treatment,” said principal investigator Victor Tapson, MD, Director, VTE and Pulmonary Vascular Disease Research Program at Cedars-Sinai Medical Center, Los Angeles, California. “The 2% one-year all-cause mortality rate observed in OPTALYSE PE is much lower than the ~8% rate seen in comparable anticoagulation studies.¹ This is important for institutions that are adopting the new low-dose, shorter duration treatments explored in OPTALYSE PE.”

The authors followed the 12-month outcomes of 101 patients at 17 centers who participated in the OPTALYSE PE study, in which the patients were randomized 1 of 4 cohorts. These patients were diagnosed with acute proximal PE in at least 1 main or proximal lobar pulmonary artery and a RV/LV diameter ratio ≥0.9 on chest computed tomographic angiography (CTA). Patients received treatment within 48 hours of diagnosis. The 4 cohorts ranged from 2-6 hours in treatment duration and 8 mg to 24 mg total tPA for bilateral PE. 

All cohorts saw a significant reduction in RV/LV by approximately 23 to 26%, taken via CTA at 48 hours. For follow-up, patients received echocardiograms at 4 hours, 48 hours, 30 days, 90 days, and at 1 year post-EKOS therapy. The initial significant reductions in RV/LV continued to improve in all cohorts through 1 year — with mean RV/LV ratios in the 0.70 range at 1 year for all cohorts. Multiple quality of life measurements showed valuable improvements between 30 days and 365 days, further demonstrating the long-term benefit of EKOS therapy. 

“EKOS is the only device cleared for the treatment of pulmonary embolism. This is the first time that long-term mortality and quality of life data has been reported for an interventional PE treatment,” said EKOS Vice President and General Manager Matt Stupfel. “Within a short time we have seen the science advance so that patients today can be treated in as little as 2 hours and with total tPA doses as low as 8 mg.” 

A separate registry study, KNOCOUT PE, is currently underway to measure how hospitals are adopting and benefiting from the new standard of care. At full enrollment, the KNOCOUT PE study is expected to include as many as 100 centers internationally. Cases will include those from before and after the release of the original OPTALYSE PE study. Physicians seeking to participate in the KNOCOUT PE study or to learn more should contact the BTG IV Clinical Affairs department.

About the EkoSonic Endovascular System

The EKOS system uses ultrasonic waves in combination with clot-dissolving thrombolytic drugs to effectively dissolve clots and restore healthy heart function and blood flow. In clinical studies, EKOS therapy has been shown to speed time-to-clot dissolution, increase clot removal, and enhance clinical improvement compared to either standard catheter-directed drug therapy or thrombectomy. EKOS therapy requires significantly shorter treatment times and less thrombolytic compared to standard catheter-directed drug therapy, lowering the risk of bleeding and other complications.

About the OPTALYSE PE, ULTIMA and SEATTLE II studies

The OPTALYSE PE, ULTIMA and SEATTLE II studies were multicenter trials examining ultrasound-facilitated, catheter-directed thrombolysis using a low dose of a tissue plasminogen activator (tPA) to treat both acute massive and submassive pulmonary embolism. ULTIMA, a randomized, controlled study comparing EKOS therapy to anticoagulation, looked at 59 patients across eight centers. SEATTLE II, a prospective, single-arm study, looked at 150 patients across 22 centers. OPTALYSE PE included 101 patients with acute proximal PE at 17 centers randomized to one of four treatment cohorts. The first cohort received 4 mg of tPA per catheter over two hours. The second cohort received 4 mg of tPA per catheter over four hours. The third cohort received 6 mg of tPA per catheter over six hours. The fourth cohort received 12 mg of tPA per catheter over six hours. All cohorts saw a significant reduction in the main indicator of right heart strain from PE (measured as RV/LV diameter ratio) by approximately 23 to 26%. The OPTALYSE PE results also showed a very low bleeding rate of three percent compared to 10% in the previous SEATTLE II study where patients were treated with 24 mg for 12 or 24 hours. n

Reference

1. Konstantinides SV, Vicaut E, Danays T, et al. Impact of thrombolytic therapy on the long-term outcome of intermediate-risk pulmonary embolism. J Am Coll Cardiol. 2017 Mar 28; 69(12): 1536-1544. doi: 10.1016/j.jacc.2016.12.039.