Acute Pulmonary Embolism, Massive Pulmonary Embolism, Pulmonary Embolism, Pulmonary Thromboembolism, Sub-massive Pulmonary Embolism
Conditions
Keywords
Fibrinolysis, catheter directed fibrinolysis, ultrasound accelerated fibrinolysis, recombinant t-PA, Activase
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.
Interventions
Participants will receive 24 mg of r-tPA delivered via the EkoSonic Endovascular Device.
DEVICEEKOS EkoSonic Endovascular System
24 mg of r-tPA will be delivered through the EkoSonic Endovascular System.
Sponsors
EKOS Corporation
Boston Scientific Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EkoSonic® Endovascular System Participants received a total of 24 mg of r-tPA infusion at an infusion rate of 1 mg/hr per device (2 mg/hour for bilateral PE) delivered through the EkoSonic® Endovascular System. This regimen allowed for a r-tPA infusion time of 24 hours for one catheter and 12 hours for two catheters, respectively. | 150 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death during catheter placement | 1 |
| Overall Study | Protocol Violation | 4 |
Baseline characteristics
| Characteristic | EkoSonic® Endovascular System |
|---|---|
| Age, Continuous | 59.0 Years STANDARD_DEVIATION 16.1 |
| Race/Ethnicity, Customized African American, Not of Hispanic Origin | 22 Participants |
| Race/Ethnicity, Customized Caucasian, Not of Hispanic Origin | 119 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 9 Participants |
| Sex: Female, Male Female | 73 Participants |
| Sex: Female, Male Male | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 59 / 150 |
| serious Total, serious adverse events | 28 / 150 |
Outcome results
Primary
Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio 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.
Time frame: Baseline, within 48 +/- 6 hours of initiation of therapy
Population: Efficacy analysis set included all participants who started the ultrasound accelerated thrombolysis therapy. Here, 'Overall number of participants analyzed' signifies participants with available data at both baseline and post-baseline. 'Number analyzed' signifies participants with available data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EkoSonic® Endovascular System | Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio Within 48 +/- 6 Hours of Initiation of Therapy | Baseline | 1.55 ratio | Standard Deviation 0.39 |
| EkoSonic® Endovascular System | Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio Within 48 +/- 6 Hours of Initiation of Therapy | Change within 48 +/- 6 hours | -0.42 ratio | Standard Deviation 0.36 |
Primary
Number of Participants With Major Bleeding
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.
Time frame: From start of study drug infusion up to 72 hours
Population: Safety analysis set included all participants who started the EkoSonic device placement procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EkoSonic® Endovascular System | Number of Participants With Major Bleeding | 14 Participants |
Secondary
Change From Baseline in Pulmonary Artery Systolic Pressure at 48 Hours After Start 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.
Time frame: Baseline, Hour 48 after initiation of therapy
Population: Efficacy analysis set included all participants who started the ultrasound accelerated thrombolysis therapy. Here, 'Number analyzed' signifies participants with available data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EkoSonic® Endovascular System | Change From Baseline in Pulmonary Artery Systolic Pressure at 48 Hours After Start of Therapy | Baseline | 51.4 millimeters of mercury (mmHg) | Standard Deviation 16 |
| EkoSonic® Endovascular System | Change From Baseline in Pulmonary Artery Systolic Pressure at 48 Hours After Start of Therapy | Change at Hour 48 | -14.4 millimeters of mercury (mmHg) | Standard Deviation 15.4 |
Secondary
Number of Devices That Could Not be Successfully Used for Infusion
Technical complications associated with the use of the EkoSonic device was recorded during catheter placement in the pulmonary artery and during the infusion procedure.
Time frame: Baseline up to Day 30
Population: Safety analysis set included all participants who started the EkoSonic device placement procedure.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| EkoSonic® Endovascular System | Number of Devices That Could Not be Successfully Used for Infusion | 7 devices |
Secondary
Number of Participants Who Died Due to Any Cause
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.
Time frame: Baseline up to Day 30
Population: Efficacy analysis set included all participants who started the ultrasound accelerated thrombolysis therapy. One participant was excluded from this analysis due to lost to follow-up after discharge.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EkoSonic® Endovascular System | Number of Participants Who Died Due to Any Cause | 4 Participants |
Secondary
Percentage of Participants With Symptomatic Recurrent Pulmonary Embolism (PE)
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.
Time frame: Baseline up to Day 30
Population: Efficacy analysis set included all participants who started the ultrasound accelerated thrombolysis therapy. One participant was excluded from this analysis due to lost to follow-up after discharge.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EkoSonic® Endovascular System | Percentage of Participants With Symptomatic Recurrent Pulmonary Embolism (PE) | 0 percentage of participants |