Trial Outcomes & Findings for Standard vs Ultrasound-assisted Catheter Thrombolysis for Submassive Pulmonary Embolism (NCT NCT03086317)

NCT ID: NCT03086317

Last Updated: 2023-06-27

Results Overview

Computed tomography angiography (CTA) will be performed before and after treatment. An independent radiologist will quantify the degree of obstruction from the thrombus by determining the vascular obstruction index. For determining the CT obstruction index, the arterial tree of each lung will be considered to have 10 segmental arteries (three to the upper lobes, two to both the middle lobe and the lingula, and five to the lower lobes).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 18 participants
• Primary outcome timeframe: Baseline to end of lysis treatment (up to 72 hours)
• Results posted on: 2023-06-27

Participant Flow

Participants were recruited from Grady Health System and Emory Healthcare System in Atlanta, Georgia, USA. Participant enrollment began October 19, 2017, and all follow-ups were completed by December 8, 2020.

Participant milestones

Measure	Standard Catheter-Directed Thrombolysis Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Overall Study STARTED	10	8
Overall Study COMPLETED	10	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Standard vs Ultrasound-assisted Catheter Thrombolysis for Submassive Pulmonary Embolism

Baseline characteristics by cohort

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Total n=18 Participants Total of all reporting groups
Age, Continuous	55 years STANDARD_DEVIATION 10 • n=5 Participants	43 years STANDARD_DEVIATION 15 • n=7 Participants	50 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants
Concomitant Deep Venous Thrombosis	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Mean Oxygen at Baseline	92 percentage of oxygen saturation n=5 Participants	95 percentage of oxygen saturation n=7 Participants	94 percentage of oxygen saturation n=5 Participants
Mean Heart Rate (HR) at baseline	98 beats per minute n=5 Participants	106 beats per minute n=7 Participants	102 beats per minute n=5 Participants

PRIMARY outcome

Timeframe: Baseline to end of lysis treatment (up to 72 hours)

Computed tomography angiography (CTA) will be performed before and after treatment. An independent radiologist will quantify the degree of obstruction from the thrombus by determining the vascular obstruction index. For determining the CT obstruction index, the arterial tree of each lung will be considered to have 10 segmental arteries (three to the upper lobes, two to both the middle lobe and the lingula, and five to the lower lobes).

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Percentage of Thrombus Obstruction Baseline ratio	33 percentage of thrombus obstruction Standard Deviation 4	31 percentage of thrombus obstruction Standard Deviation 4
Percentage of Thrombus Obstruction End of lysis treatment (up to 72 hrs)	23 percentage of thrombus obstruction Standard Deviation 7	22 percentage of thrombus obstruction Standard Deviation 7

SECONDARY outcome

Timeframe: Until hospital discharge (an average of 6 days)

Mortality during hospitalization will be compared between the two study arms.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
In Hospital Mortality	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Until 90 days post procedure

Mortality until 90 days post procedure will be compared between the two study arms.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
90-day Mortality	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Through follow up (12 months)

Cardiac decompensation, defined as hypotension (<90 millimeters of mercury (mmHg)) and use of catecholamines, will be compared between the two study arms.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Cardiac Decompensation Due to Massive Pulmonary Embolism	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Through follow up (12 months)

Major bleeding is defined as overt bleeding associated with a hemoglobin level reduction of at least 2.0 grams per deciliter (g/dL), or with transfusion of two or more units of red blood cells, or involvement of a critical site (intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome).

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Major Bleeding	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Through follow up (12 months)

Clinically overt bleeding not fulfilling the criteria of major bleeding is classified as a minor bleeding complication.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Minor Bleeding	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Until 90 days post procedure

Recurrent venous thromboembolism (VTE) will be diagnosed if symptoms or signs of deep vein thrombosis or acute pulmonary embolism (PE) are confirmed by an imaging test. There will be no routine surveillance for asymptomatic recurrent VTE.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Symptomatic Venous Thromboembolism (VTE)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Until 90 days post procedure

Treatment will be considered successful if pulmonary embolism related decompensation is prevented, without the participant experiencing a major adverse event or death.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Clinical Success of Treatment	10 Participants	8 Participants

SECONDARY outcome

Timeframe: Until hospital discharge (an average of 6 days)

The number of days participants were admitted to the ICU will be compared between study arms.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
ICU Length of Stay	2 Days Interval 2.0 to 5.0	2 Days Interval 1.0 to 58.0

SECONDARY outcome

Timeframe: Baseline, end of lysis treatment, Month 3, Month 12

Population: Endpoint results include only participants who showed up for the study visits.

Under normal circumstances, the right ventricle appears smaller than the left ventricle when measured by an echocardiogram (RV/LV ratio<1). An increased RV/LV ratio may be a predictor of poor clinical outcomes following pulmonary embolism.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Change in Right Ventricular/Left Ventricular (RV/LV) Diameter Ratio Baseline (RV/LV) diameter ratio	1.7 ratio Standard Deviation 0.4	1.5 ratio Standard Deviation 0.3
Change in Right Ventricular/Left Ventricular (RV/LV) Diameter Ratio End of Lysis Treatment (RV/LV) diameter ratio	1.1 ratio Standard Deviation 0.2	1.2 ratio Standard Deviation 0.2
Change in Right Ventricular/Left Ventricular (RV/LV) Diameter Ratio Month 3	0.87 ratio Standard Deviation 0.3	0.89 ratio Standard Deviation 0.2
Change in Right Ventricular/Left Ventricular (RV/LV) Diameter Ratio Month 12	0.82 ratio Standard Deviation 0.2	0.84 ratio Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline, end of lysis treatment, Month 3, Month 12

Population: Data was not collected

Tricuspid annular plane systolic excursion (TAPSE) is an echocardiographic of measuring right ventricular function. TAPSE measurements can be categorized as normal (1.5-2.0cm), mildly abnormal (1.3-1.5cm), moderately abnormal (1.0-1.2cm) or severely abnormal (<1.0cm).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, end of lysis treatment, Month 3, Month 12

Population: Results reflect participants who completed study procedures during each study visit

Right ventricular systolic pressure (RVSP) measured by echocardiogram provides an estimate the pressure inside the artery supplying blood to the lungs. Dysfunction in the right ventricle is assessed to predict clinical outcomes following pulmonary embolism.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=10 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=8 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Change in Right Ventricular Systolic Pressure (RVSP) Baseline	55 mmHg Standard Deviation 14	50 mmHg Standard Deviation 10
Change in Right Ventricular Systolic Pressure (RVSP) End of lysis Treatment	42 mmHg Standard Deviation 0	38 mmHg Standard Deviation 0
Change in Right Ventricular Systolic Pressure (RVSP) Month 3	36 mmHg Standard Deviation 12	37 mmHg Standard Deviation 19
Change in Right Ventricular Systolic Pressure (RVSP) Month 12	32 mmHg Standard Deviation 10	34 mmHg Standard Deviation 16

SECONDARY outcome

Timeframe: Month 3, Month 12

Population: All participants had a baseline NYHA Class 4

New York Heart Association (NYHA) Functional Classification of heart failure classifies heart failure with a combination of two methods: patient symptoms and objective assessment by a healthcare provider. Patient symptoms are classified as I-IV, where I = "no limitation of physical activity" and IV = "unable to carry on any physical activity without discomfort". An objective assessment by a healthcare provider is classified as A through D where A = "objective evidence of cardiovascular disease" and D = "objective evidence of severe cardiovascular disease".

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=6 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=5 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Number of Participants Who Had a Decrease in New York Heart Association (NYHA) Functional Classification of Heart Failure From Class 4 to Class 2 Month 3- Number of participants with NYHA Class 2	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Month 3, Month 12

The 6-minute walk test (6MWT) measures the distance that can be quickly walked by the study participant in 6 minutes. A 30 meter long walking course is created using cones on a hard, flat surface and the participant will walk the course as many times as they can in 6 minutes while a study team member counts the number of laps completed. Specific test guidelines from the American Thoracic Society will be followed.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=7 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=2 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Change in 6-minute Walk Test Month 3	360 meters Standard Deviation 131	330 meters Standard Deviation 28
Change in 6-minute Walk Test Month 12	336 meters Standard Deviation 14	387 meters Standard Deviation 92

SECONDARY outcome

Timeframe: Month 3, Month 12

The SF-36 is a 36 item survey assessing the quality of life across the 8 domains of physical functioning, limitations due to physical health, limitations due to emotional health, energy, emotional well-being, social functioning, pain, and general health. Each item is scored between 0 and 100 where 0 represents the worst possible quality of life and 100 corresponds with a healthy state of being. The numbers analyzed below represent the average score obtained with 0 being the bottom 25% of the quality of life (score 0-25), 1 is 26-50, 2 is 51-75, and 4 is 76-100.

Outcome measures

Measure	Standard Catheter-Directed Thrombolysis n=7 Participants Participants randomized to this arm will receive standard catheter-directed thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Standard Catheter-Directed Thrombolysis: Catheter-directed thrombolysis requires placement of a multi-sidehole infusion catheter within the pulmonary arterial thrombus burden, under angiographic guidance. Thrombolytic medications are slowly infused through the catheter, which is left in place for the duration of the treatment. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.	Ultrasound-Accelerated Thrombolysis n=5 Participants Participants randomized to this arm will receive ultrasound-accelerated thrombolysis, per standard of care, as treatment for acute submassive pulmonary embolism. Ultrasound-Accelerated Thrombolysis: USAT is a modification of standard catheter-directed thrombolysis utilizing a proprietary system of local high frequency, low-power ultrasound to dissociate the fibrin matrix of the thrombus, allowing deeper penetration of lytic medication. The treatment will be performed according to current standard of care and all technical considerations will be left to the discretion of the operator performing the procedure. All follow up is according to standard of care.
Change in 36-Item, Short Form (SF-36) Score Month 3	3.1 score on a scale Standard Deviation 0.94	3.17 score on a scale Standard Deviation 0.69
Change in 36-Item, Short Form (SF-36) Score Month 12	3.43 score on a scale Standard Deviation 0.73	3.6 score on a scale Standard Deviation 0.49

SECONDARY outcome

Timeframe: Month 3, Month 12

Population: Data not collected

Quality of life after pulmonary embolism (PEmb QoL) questionnaire is a 40 item survey asking respondents about their lung symptoms after having a pulmonary embolism. Participants report on 6 dimensions which cover the frequency and intensity of lung symptoms, physical and social limitations due to symptoms, pain, and emotional distress following having a pulmonary embolism. Scoring the responses involves specific instructions to reverse the scores for several dimensions, resulting in a score between 0 and 100 where 0 corresponds with "no complaints" and 100 is "worst possible" outcome.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 3, Month 12

Population: Data was not collected

The University of California San Diego (UCSD) Medical Center Shortness of Breath Questionnaire is a 24 item survey asking respondents how much shortness of breath they experience doing particular activities. Breathlessness is rated on a scale of 0 (not at all breathless) to 5 (maximally breathless or unable to do an activity become of breathlessness). Total scores range from 0 to 120, with higher scores indicating increased shortness of breath.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 12

Population: Data was not collected

A Markov state-transition, cost effectiveness model will be created to simulate patient oriented outcomes assuming a societal perspective with a 12-month time horizon. All point estimates for model parameters will be determined from the prospectively collected data. Quality adjusted life years will be determined for each therapy based on survival, freedom from major adverse events, discharge status, functional status, and quality of life measures. Costs will be calculated for each therapy based on in-hospital resource utilization (i.e., length of stay in the ICU, operating room and procedure costs, and associated adverse event costs) and out-of-hospital costs (outpatient nursing care, loss of work, outpatient testing and follow-up).

Outcome measures

Outcome data not reported

Adverse Events

Standard Catheter-Directed Thrombolysis

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Ultrasound-Accelerated Thrombolysis

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Wissam Jaber, Assistant Professor

Emory University

Phone: 4046861000

Email: wissam.jaber@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place