Submassive and Massive Pulmonary Embolism Treatment With Ultrasound Accelerated Thrombolysis Therapy

Phase 3

Completed

Conditions: Sub-massive Pulmonary Embolism
Massive Pulmonary Embolism
Pulmonary Thromboembolism
Pulmonary Embolism
Acute Pulmonary Embolism

Interventions: Drug: recombinant tissue plasminogen activator
Device: EKOS EkoSonic Endovascular System

Registration Number: NCT01513759

Lead Sponsor: Boston Scientific Corporation

Brief Summary: The purpose of this study is to determine if the EKOS EkoSonic® Endovascular Device when used in conjunction with recombinant tissue plasminogen activator (t-PA) as a treatment for acute PE will decrease the ratio of right ventricle (RV) to left ventricle (LV) diameter within 48 =/- 6 hours in participants with massive or submassive PE.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 150

Inclusion Criteria

Computed tomography (CT) evidence of proximal PE (filling defect in at least one main or segmental pulmonary artery)
PE symptom duration less than or equal to (<=)14 days
Informed consent can be obtained from participant or Legally Authorized Representative (LAR)
Massive PE (syncope, systemic arterial hypotension, cardiogenic shock, or resuscitated cardiac arrest) or
Submassive PE (RV diameter-to-LV diameter greater than or equal to [>=] 0.9 on contrast-enhanced chest CT)

Exclusion Criteria

Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year
Recent (within one month) or active bleeding from a major organ
Hematocrit less than (<) 30 percent (%)
Platelets < 100 thousand/microliter (mcL)
International Normalized Ratio (INR) greater than (>) 3
Activated partial thromboplastin time (aPTT) >50 seconds on no anticoagulants
Major surgery within seven days of screening for study enrollment
Serum creatinine >2 milligrams/deciliter (mg/dL)
Clinician deems high-risk for catastrophic bleeding
History of heparin-induced thrombocytopenia (HIT)
Pregnancy
Catheter-based pharmacomechanical treatment for pulmonary embolism within 3 days of study enrollment
Systolic blood pressure less than 80 mm Hg despite vasopressor or inotropic support
Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR)
Evidence of irreversible neurological compromise
Life expectancy <30 days
Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to inclusion in the study
Previous enrollment in the SEATTLE study

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EkoSonic® Endovascular System	recombinant tissue plasminogen activator	Participants will receive a total of 24 milligrams (mg) of recombinant t-PA infusion, at an infusion rate of 1 milligrams/hour (mg/hr) per device (2 mg/hour for bilateral PE) delivered through the EkoSonic® Endovascular System. This regimen allows for a recombinant t-PA infusion time of 24 hours for one catheter and 12 hours for two catheters, respectively.
EkoSonic® Endovascular System	EKOS EkoSonic Endovascular System	Participants will receive a total of 24 milligrams (mg) of recombinant t-PA infusion, at an infusion rate of 1 milligrams/hour (mg/hr) per device (2 mg/hour for bilateral PE) delivered through the EkoSonic® Endovascular System. This regimen allows for a recombinant t-PA infusion time of 24 hours for one catheter and 12 hours for two catheters, respectively.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Major Bleeding	From start of study drug infusion up to 72 hours	Bleeding adverse events were graded (severe or life-threatening, moderate or mild bleeding) according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification. The participant incidence of major bleeding events was defined as GUSTO moderate and severe events occurring within 72 hours after starting the ultrasound-accelerated catheter-directed fibrinolysis procedure. Mild: Does not meet criteria for moderate or severe; Moderate: Requires transfusion - No hemodynamic compromise; and Severe: Bleeding causes hemodynamic compromise and required intervention or intracranial hemorrhage. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio Within 48 +/- 6 Hours of Initiation of Therapy	Baseline, within 48 +/- 6 hours of initiation of therapy	Change from baseline in RV diameter/LV diameter ratio was determined by contrast-enhanced chest computed tomography (CT) within 48 +/- 6 hours after initiating ultrasound-accelerated catheter-directed fibrinolysis.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Pulmonary Artery Systolic Pressure at 48 Hours After Start of Therapy	Baseline, Hour 48 after initiation of therapy	Change in pulmonary artery systolic pressure was assessed by baseline right-heart catheterization compared with right-heart catheterization at the conclusion of ultrasound-accelerated catheter-directed fibrinolysis and estimated by post-procedure transthoracic echocardiography within 48 hours after initiating the procedure.
Percentage of Participants With Symptomatic Recurrent Pulmonary Embolism (PE)	Baseline up to Day 30	Percentage of participants with symptomatic recurrent PE up to 30 days following the conclusion of the ultrasound-accelerated catheter-directed fibrinolysis procedure, were reported with a Wilson score 95% confidence interval. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Number of Participants Who Died Due to Any Cause	Baseline up to Day 30	Number of participants who died due to any cause for up to 30 days following the conclusion of the ultrasound-accelerated catheter-directed fibrinolysis procedure, were reported.
Number of Devices That Could Not be Successfully Used for Infusion	Baseline up to Day 30	Technical complications associated with the use of the EkoSonic device was recorded during catheter placement in the pulmonary artery and during the infusion procedure.

Trial Locations

Locations (22): Orlando Regional Medical Center
🇺🇸
Orlando, Florida, United States
Florida Hospital
🇺🇸
Orlando, Florida, United States
Christiana Hospital
🇺🇸
Newark, Delaware, United States
East Jefferson General Hospital
🇺🇸
New Orleans, Louisiana, United States
Lakeland Regional Medical Center
🇺🇸
Lakeland, Florida, United States
Holmes Regional Medical Center
🇺🇸
Melbourne, Florida, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Overlook Medical Center
🇺🇸
Morristown, New Jersey, United States
Holy Name Hospital
🇺🇸
Teaneck, New Jersey, United States
Providence Memorial and Sierra Medical Center
🇺🇸
El Paso, Texas, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
Memorial Medical Center
🇺🇸
Modesto, California, United States
Inova Alexandria Hospital
🇺🇸
Alexandria, Virginia, United States
Baptist Health
🇺🇸
Montgomery, Alabama, United States
Stanford University Medical Center
🇺🇸
Stanford, California, United States
Medical Center of Central Georgia
🇺🇸
Macon, Georgia, United States
Prairie Heart Institute
🇺🇸
Springfield, Illinois, United States
Mt. Carmel East
🇺🇸
Columbus, Ohio, United States
The Miriam Hospital
🇺🇸
Providence, Rhode Island, United States
St. Vincent Hospital
🇺🇸
Indianapolis, Indiana, United States
University of Kentucky, Gill Heart Institute
🇺🇸
Lexington, Kentucky, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States