A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study

JACC Cardiovasc Interv. 2015 Aug 24;8(10):1382-92. doi: 10.1016/j.jcin.2015.04.020.

Abstract

Objectives: This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington).

Background: Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%.

Methods: Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation.

Results: Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage.

Conclusions: Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

Keywords: catheter embolectomy; catheter thrombolysis; fibrinolysis; pulmonary embolism; right ventricular failure; thrombolysis.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Catheterization, Peripheral* / adverse effects
  • Catheterization, Peripheral* / instrumentation
  • Catheterization, Peripheral* / mortality
  • Equipment Design
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Hemorrhage / chemically induced
  • Humans
  • Hypertension, Pulmonary / etiology
  • Hypertrophy, Right Ventricular / etiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Embolism / complications
  • Pulmonary Embolism / diagnosis
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / mortality
  • Risk Factors
  • Severity of Illness Index
  • Thrombolytic Therapy* / adverse effects
  • Thrombolytic Therapy* / instrumentation
  • Thrombolytic Therapy* / mortality
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Ultrasonic Therapy* / adverse effects
  • Ultrasonic Therapy* / instrumentation
  • Ultrasonic Therapy* / mortality
  • United States
  • Vascular Access Devices

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator

Associated data

  • ClinicalTrials.gov/NCT01513759