SEATTLE II: Submassive and Massive Pulmonary Embolism Treatment With Ultrasound Accelerated Thrombolysis Therapy

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01513759
• Collaborator: EKOS Corporation (Industry)
• Enrollment: 150
• Locations: 22
• Arm: 1
• Actual Duration (Months): 8.4
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Embolism; Acute Pulmonary Embolism; Sub-massive Pulmonary Embolism; Massive Pulmonary Embolism; Pulmonary Thromboembolism	Drug: recombinant tissue plasminogen activator; Device: EKOS EkoSonic Endovascular System	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Single-Arm, Multi-Center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE)
• Actual Study Start Date: Jun 7, 2012
• Actual Primary Completion Date: Feb 17, 2013
• Actual Study Completion Date: Feb 17, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: recombinant tissue plasminogen activator; Participants will receive 24 mg of r-tPA delivered via the EkoSonic Endovascular Device.; Other Names: r-tPA t-PA Alteplase ; Device: EKOS EkoSonic Endovascular System; 24 mg of r-tPA will be delivered through the EkoSonic Endovascular System.; Other Names: EkoSonic Endovascular Device EkoSonic

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baptist Health	Montgomery	Alabama	United States	36116
2	Memorial Medical Center	Modesto	California	United States	95355
3	Stanford University Medical Center	Stanford	California	United States	94305
4	Hartford Hospital	Hartford	Connecticut	United States
5	Christiana Hospital	Newark	Delaware	United States	19718
6	Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
7	Holmes Regional Medical Center	Melbourne	Florida	United States	32901
8	Florida Hospital	Orlando	Florida	United States	32803
9	Orlando Regional Medical Center	Orlando	Florida	United States	32806
10	Medical Center of Central Georgia	Macon	Georgia	United States	31201
11	Prairie Heart Institute	Springfield	Illinois	United States	62701
12	St. Vincent Hospital	Indianapolis	Indiana	United States
13	University of Kentucky, Gill Heart Institute	Lexington	Kentucky	United States	40536
14	East Jefferson General Hospital	New Orleans	Louisiana	United States	70006
15	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
16	Overlook Medical Center	Morristown	New Jersey	United States	07960
17	Holy Name Hospital	Teaneck	New Jersey	United States	07666
18	Montefiore Medical Center	Bronx	New York	United States	10467
19	Mt. Carmel East	Columbus	Ohio	United States	43213
20	The Miriam Hospital	Providence	Rhode Island	United States	02906
21	Providence Memorial and Sierra Medical Center	El Paso	Texas	United States	79902
22	Inova Alexandria Hospital	Alexandria	Virginia	United States	22304

Sponsors and Collaborators

• Boston Scientific Corporation
• EKOS Corporation

Investigators

• Principal Investigator: Narinder Bhalla, MD, Baptist Health
• Principal Investigator: William Kuo, MD, Stanford Hospital and Clinics
• Principal Investigator: Stephen K Liu, MD, Memorial Medical Center - Modesto
• Principal Investigator: Immad Sidiq, MD, Hartford Hospital
• Study Chair: Samuel Z Goldhaber, MD, Brigham and Women's
• Principal Investigator: Mark J Garcia, MD, Christiana Hospital
• Principal Investigator: Rohit Bhatheja, MD, AdventHealth
• Principal Investigator: Robert Kennedy, MD, Holmes Regional Medical Center
• Principal Investigator: Fakhir Elmasri, MD, Lakeland Regional Medical Center
• Principal Investigator: Barry S Weinstock, MD, Orlando Regional Medical Center
• Principal Investigator: Juan Ayerdi, MD, Medical Center of Central Georgia
• Principal Investigator: Nilesh Goswami, MD, Prairie Heart Institute - St.John's Hospital
• Principal Investigator: Kannan Natarajan, MD, St. Vincent's Hospital-Manhattan
• Principal Investigator: Tod C Engelhardt, MD, East Jefferson General Hospital
• Principal Investigator: Mark Kumar, MD, Overlook Medical Center
• Principal Investigator: John Rundback, MD, Holy Name Hospital
• Principal Investigator: Jacob Cynamon, MD, Montefiore Medical Center
• Principal Investigator: Peter Soukas, MD, The Miriam Hospital
• Principal Investigator: Mohammad L Raja, MD, Providence Memorial Hospital - Sierra Vista Hospital
• Principal Investigator: Keith M Sterling, MD, Inova Alexandria
• Principal Investigator: John Gurley, MD, University of Kentucky
• Principal Investigator: Noah Jones, MD, Mt. Carmel East

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT01513759
• Other Study ID Numbers: EKOS 09
• First Posted: Jan 20, 2012
• Last Update Posted: Jul 19, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Boston Scientific Corporation: Fibrinolysis; catheter directed fibrinolysis; ultrasound accelerated fibrinolysis; recombinant t-PA; Activase
• Additional relevant MeSH terms: Pulmonary Embolism; Embolism; Thromboembolism; Tissue Plasminogen Activator; Plasminogen

Study Results

Participant Flow

Arm/Group Title	EkoSonic® Endovascular System
Arm/Group Description	Participants received a total of 24 milligrams (mg) of recombinant tissue plasminogen activator (r-tPA) infusion, at an infusion rate of 1 milligrams/hour (mg/hr) per device (2 mg/hour for bilateral pulmonary embolism [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.
Period Title: Overall Study
STARTED	150
At Least One Device Successfully Placed	149
COMPLETED	145
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	EkoSonic® Endovascular System
Arm/Group Description	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.
Overall Participants	150
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.0 (16.1)
Sex: Female, Male (Count of Participants)
Female	73 48.7%
Male	77 51.3%
Race/Ethnicity, Customized (Count of Participants)
Caucasian, Not of Hispanic Origin	119 79.3%
African American, Not of Hispanic Origin	22 14.7%
Hispanic or Latino	9 6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio Within 48 +/- 6 Hours of Initiation of Therapy
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	EkoSonic® Endovascular System
Arm/Group Description	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.
Measure Participants	150
Baseline	1.55 (0.39)
Change within 48 +/- 6 hours	-0.42 (0.36)

2. Primary Outcome

Title	Number of Participants With Major Bleeding
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who started the EkoSonic device placement procedure.

Arm/Group Title	EkoSonic® Endovascular System
Arm/Group Description	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.
Measure Participants	150
Count of Participants [Participants]	14 9.3%

3. Secondary Outcome

Title	Change From Baseline in Pulmonary Artery Systolic Pressure at 48 Hours After Start of Therapy
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	EkoSonic® Endovascular System
Arm/Group Description	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.
Measure Participants	150
Baseline	51.4 (16)
Change at Hour 48	-14.4 (15.4)

4. Secondary Outcome

Title	Percentage of Participants With Symptomatic Recurrent Pulmonary Embolism (PE)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	EkoSonic® Endovascular System
Arm/Group Description	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.
Measure Participants	149
Number (95% Confidence Interval) [percentage of participants]	0 0%

5. Secondary Outcome

Title	Number of Participants Who Died Due to Any Cause
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	EkoSonic® Endovascular System
Arm/Group Description	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.
Measure Participants	149
Count of Participants [Participants]	4 2.7%

6. Secondary Outcome

Title	Number of Devices That Could Not be Successfully Used for Infusion
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who started the EkoSonic device placement procedure.

Arm/Group Title	EkoSonic® Endovascular System
Arm/Group Description	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.
Measure Participants	150
Measure devices	285
Count of Units [devices]	7

Adverse Events

Time Frame	Baseline up to Day 30
Adverse Event Reporting Description	Safety analysis set included all participants who started the EkoSonic device placement procedure.
Arm/Group Title	EkoSonic® Endovascular System
Arm/Group Description	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.
All Cause Mortality
	EkoSonic® Endovascular System
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	EkoSonic® Endovascular System
	Affected / at Risk (%)	# Events
Total	28/150 (18.7%)
Blood and lymphatic system disorders
Anemia	3/150 (2%)
Heparin-induced thrombocytopenia	1/150 (0.7%)
Haemorrhagic anaemia	1/150 (0.7%)
Cardiac disorders
Atrial flutter	1/150 (0.7%)
Atrial fibrillation	1/150 (0.7%)
Pericardial effusion	1/150 (0.7%)
General disorders
Chest Pain	1/150 (0.7%)
Infections and infestations
Sepsis	1/150 (0.7%)
Injury, poisoning and procedural complications
Vascular pseudoaneurysm	1/150 (0.7%)
Investigations
Electroencephalogram abnormal	1/150 (0.7%)
Renal and urinary disorders
Haematuria	2/150 (1.3%)
Renal failure acute	2/150 (1.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/150 (1.3%)
Dyspnoea	2/150 (1.3%)
Hypoxia	1/150 (0.7%)
Pleural effusion	1/150 (0.7%)
Pulmonary arterial hypertension	1/150 (0.7%)
Pulmonary embolism	1/150 (0.7%)
Respiratory failure	2/150 (1.3%)
Epistaxis	1/150 (0.7%)
Vascular disorders
Deep vein thrombosis	3/150 (2%)
Haematoma	3/150 (2%)
Hypotension	1/150 (0.7%)
Other (Not Including Serious) Adverse Events
	EkoSonic® Endovascular System
	Affected / at Risk (%)	# Events
Total	59/150 (39.3%)
Blood and lymphatic system disorders
Anemia	6/150 (4%)
Haemorrhagic anaemia	1/150 (0.7%)
Heparin-induced thrombocytopenia	1/150 (0.7%)
Leukocytosis	1/150 (0.7%)
Thrombocytopenia	4/150 (2.7%)
Cardiac disorders
Atrial fibrillation	2/150 (1.3%)
Ventricular arrhythmia	1/150 (0.7%)
Chest pain	1/150 (0.7%)
Pyrexia	2/150 (1.3%)
Gastrointestinal disorders
Abdominal pain	2/150 (1.3%)
Abdominal wall haematoma	1/150 (0.7%)
Constipation	2/150 (1.3%)
Diarrhoea	2/150 (1.3%)
Gastrointestinal haemorrhage	1/150 (0.7%)
Nausea	1/150 (0.7%)
Vomiting	1/150 (0.7%)
General disorders
Chest discomfort	4/150 (2.7%)
Infections and infestations
Cellulitis	2/150 (1.3%)
Pneumonia	2/150 (1.3%)
Urinary Tract Infection	5/150 (3.3%)
Injury, poisoning and procedural complications
Arterial injury	1/150 (0.7%)
Contusion	1/150 (0.7%)
Operative haemorrhage	1/150 (0.7%)
Wound secretion	1/150 (0.7%)
Investigations
Blood creatinine increased	1/150 (0.7%)
Blood glucose increased	1/150 (0.7%)
Blood pressure decreased	1/150 (0.7%)
Electrocardiogram abnormal	2/150 (1.3%)
Metabolism and nutrition disorders
Diabetes mellitus	1/150 (0.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/150 (0.7%)
Facial asymmetry	1/150 (0.7%)
Groin pain	1/150 (0.7%)
Muscle haemorrhage	1/150 (0.7%)
Pain in extremity	1/150 (0.7%)
Musculoskeletal stiffness	1/150 (0.7%)
Nervous system disorders
Convulsion	1/150 (0.7%)
Psychiatric disorders
Mental status changes	1/150 (0.7%)
Renal and urinary disorders
Haematuria	1/150 (0.7%)
Renal failure acute	3/150 (2%)
Renal failure chronic	2/150 (1.3%)
Nephrolithiasis	1/150 (0.7%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	3/150 (2%)
Dyspnoea	2/150 (1.3%)
Haemoptysis	5/150 (3.3%)
Oropharyngeal pain	1/150 (0.7%)
Pleural effusion	3/150 (2%)
Pulmonary oedema	1/150 (0.7%)
Skin and subcutaneous tissue disorders
Ecchymosis	2/150 (1.3%)
Rash erythematous	1/150 (0.7%)
Vascular disorders
Haematoma	10/150 (6.7%)
Deep vein thrombosis	3/150 (2%)
Hypertension	1/150 (0.7%)
Hypotension	1/150 (0.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.