A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial

JACC Cardiovasc Interv. 2018 Jul 23;11(14):1401-1410. doi: 10.1016/j.jcin.2018.04.008.


Objectives: The aim of this study was to determine the lowest optimal tissue plasminogen activator (tPA) dose and delivery duration using ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk (submassive) pulmonary embolism.

Background: Previous trials of USCDT used tPA over 12 to 24 h at doses of 20 to 24 mg for acute pulmonary embolism.

Methods: Hemodynamically stable adults with acute intermediate-risk pulmonary embolism documented by computed tomographic angiography were randomized into this prospective multicenter, parallel-group trial. Patients received treatment with 1 of 4 USCDT regimens. The tPA dose ranged from 4 to 12 mg per lung and infusion duration from 2 to 6 h. The primary efficacy endpoint was reduction in right ventricular-to-left ventricular diameter ratio by computed tomographic angiography. A major secondary endpoint was embolic burden by refined modified Miller score, measured on computed tomographic angiography 48 h after initiation of USCDT.

Results: One hundred one patients were randomized, and improvements in right ventricular-to-left ventricular diameter ratio were as follows: arm 1 (4 mg/lung/2 h), 0.40 (24%; p = 0.0001); arm 2 (4 mg/lung/4 h), 0.35 (22.6%; p = 0.0001); arm 3 (6 mg/lung/6 h), 0.42 (26.3%; p = 0.0001); and arm 4 (12 mg/lung/6 h), 0.48 (25.5%; p = 0.0001). Improvement in refined modified Miller score was also seen in all groups. Four patients experienced major bleeding (4%). Of 2 intracranial hemorrhage events, 1 was attributed to tPA delivered by USCDT.

Conclusions: Treatment with USCDT using a shorter delivery duration and lower-dose tPA was associated with improved right ventricular function and reduced clot burden compared with baseline. The major bleeding rate was low, but 1 intracranial hemorrhage event due to tPA delivered by USCDT did occur.

Keywords: catheter-directed therapy; fibrinolysis; pulmonary embolism; right ventricular failure; thrombolysis.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Europe
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Intracranial Hemorrhages / chemically induced
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Embolism / diagnostic imaging
  • Pulmonary Embolism / physiopathology
  • Pulmonary Embolism / therapy*
  • Recovery of Function
  • Risk Factors
  • Thrombolytic Therapy* / adverse effects
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects
  • Treatment Outcome
  • Ultrasonic Therapy* / adverse effects
  • United States
  • Ventricular Function, Right


  • Fibrinolytic Agents
  • Tissue Plasminogen Activator