Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Pulmonary Embolism

Percentage of Participants With Treatment Success of an APT Procedure

Treatment success of an APT procedure will be assessed by an Adjudication Committee that is blinded to the participant's treatment. The criteria for treatment success are defined as follows: A decrease in RV/LV from baseline to 48 hours after the start of the procedure of at least 0.2; and no life-threatening adverse events related to PE or its treatment through 30 days after the start of the APT procedure.

Time frame: From Baseline up to Day 30

Change From Baseline in RV/LV at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph.

An echocardiogram was obtained at specified timepoints to evaluate RV/LV.

Time frame: Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

The extent of displacement of the tricuspid valves, termed as TAPSE was measured at specified timepoints using echocardiogram.

Time frame: Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

Change From Baseline in Estimated Right Ventricular Systolic Pressure (RVSP) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

RVSP was measured at specified timepoints using echocardiogram.

Time frame: Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

Percentage of Participants With Collapse of the Inferior Vena Cava (IVC) With Respiration at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph

The collapse of IVC was measured at specified timepoints using echocardiogram.

Time frame: Baseline (Day -2 [within -48 hrs of APT start]), Day 0 (within 4 hours after APT end), Day 2 (48 [± 6] hrs of APT start), Day 30 (± 5 days), Day 90 (± 10 days) and Day 365 (± 14 days)

Change From Baseline in Thrombus Burden by Miller Score as Assessed by Pulmonary Arteriogram (PAgram) at Day 0

Miller score is composed of a score for arterial obstruction (objective score) and a score for reduction of peripheral perfusion of lungs (subjective evaluation). Right pulmonary artery (PA) is assigned 9 segmental arteries (3 to the upper, 2 to the middle, and 4 to the lower lobe), and left PA is assigned only 7 segmental arteries (2 to the upper, 2 to the lingula, and 3 to the lower lobe). Presence of segmental emboli, regardless of the degree of obstruction, is scored 1 point. Proximal emboli to the segmental level are scored a value equal to the number of segmental arteries arising distally. Maximal score of obstruction=16. Reduction of peripheral perfusion is scored by dividing each lung into upper, middle, and lower zones and by using a 4-point scale: 0=normal perfusion; 1=moderately reduced perfusion; 2=severely reduced perfusion; 3=no perfusion. Maximal score of reduced perfusion=18. Thus, the maximal Miller score =34. Higher Miller score=more thrombus burden.

Time frame: Baseline, Day 0 (within 4 hours after APT end)

Change From Baseline in Thrombus Burden by Modified Miller Score as Assessed by CTA Scan at 48 ± 6 Hours After the Start of the APT Procedure

Modified miller score quantifies thrombus burden on CTA scans. Each segmental pulmonary artery (9 on the right, 7 on the left) that is fully or partly occluded by thrombus is given a score of 1. Any further proximal involves vessels score the number of segmental branches distal to that vessel, thereby giving a modified miller score of 0 (no thrombus) to 16 (thrombus in all segmental arteries or saddle embolism).

Time frame: From Baseline to 48 hrs ± 6 hours

Change in 6 Minute Walk (6MW) Distance From Day 30 to Day 90 and 365

The 6 minute Walk Test is a measure of functional exercise capacity. Participants will be asked to walk as far as possible within a 6-minute period, and the distance covered at the end will be noted and recorded.

Time frame: Days 30, 90, 365

Change in Borg Scale Score Before and After 6MW Distance Test at Days 30, 90, and 365

Borg is a 10-point scale rating the maximum level of dyspnea (difficulty in breathing) and fatigue experienced before and after the 6MW distance test. Scores ranges from 0 (for no shortness of breath, or no fatigue) to 10 (for the greatest shortness of breath ever experienced, or maximum amount of fatigue felt). Higher scores indicates worse outcome.

Time frame: Days 30, 90, and 365

Number of Participants Who Received Oxygen Therapy

Oxygen source is categorized as room air, nasal prongs, mask, and intubated.

Time frame: Days 30, 90, and 365

Change in Participant Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) 6b Score From Day 30 to Day 365

PROMIS-PF 6b questionnaire is developed by including 2-items from item-improved Health Assessment Questionnaire (HAQ) and 4-items from item-improved Physical Function-10 (PF-10) instruments. Both of these instruments assess participant's present abilities. Both "Item-Improved instruments" have 5-response options: HAQ - 1="without any difficulty," 2="with a little difficulty," 3="with some difficulty," 4="with much difficulty," 5="unable to do"; PF-10 - 1="not at all," 2="very little," 3="somewhat," 4="quite a lot," 5="cannot do." Total score is the average of all scores of component items, which ranges from 0 (no disability) to 100 (worst disability).

Time frame: Day 30, Day 365

Change in Pulmonary Embolism Quality of Life (PEmb-QOL) Score From Day 30 to Day 365

The PEmb-QoL questionnaire contains 6 dimensions that has been created based on the contents of the items, frequency of complaints (Question \[Q\]1; score range: 1 \[every day\] to 5 \[never\]), activities of daily living (ADL) limitations (Q4; score range: 1 \[limited a lot\] to 3 \[not at all\]), work-related problems (Q5; response: yes/no), social limitations (Q6; score range: 1 \[not at all\] to 5 \[extremely\]), intensity of complaints (Q7 \[pain in chest/shoulders\]/8 \[breathlessness\]; score range: 1 \[none\] to 6 \[very serious\]) and emotional complaints (Q9; score range: 1 \[at all times\] to 6 \[none of the times\]). Total Score for all dimensions are calculated by the sum of the scores for each item of the dimension divided by the number of items. Total score ranges from 1 (better quality of life) to 100 (worst quality of life). Higher scores indicate poorer outcome (decreased quality of life). Questions 1, 4, 5, and 9 are reverse scored. Questions 2 and 3 provide descriptive information.

Time frame: Day 30, Day 365

Number of Participants Who Encountered Technical Procedural Complications

Technical complications associated with the use of the EKOS device will be recorded during catheter placement in the pulmonary artery and during the infusion procedure.

Time frame: From device placement through Day 2

Number of Participants With Symptomatic Recurrent Pulmonary Embolism (Per Adjudication)

Number of participants with symptomatic recurrent pulmonary embolism up to 365 days following the APT procedure, were reported. 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 Baseline up to Day 365

Number of Participants Who Die Due to Any Cause

Number of participants who died due to any cause for up to 365 days following the APT procedure, were reported.

Time frame: From Baseline up to Day 365

For Participants of UK Sites: Freedom From Major Harm Occurring Between Enrolment and 30 Days

Number of UK participants with freedom from major harms assessed by Safety Monitor using the following criteria: 1) Mortality - all cause and PE related; 2) Cardiovascular (CV) collapse defined as one or more of the following: a) Greater than (\>) 40 millimeters of mercury (mmHg) drop in systolic blood pressure (SBP) (for \>15 minutes from documented blood pressure as an in-patient) despite intravenous (IV) fluid challenge and absence of new atrial arrhythmia; b) Requirement for emergency systemic thrombolysis; c) Requirement for emergency surgical embolectomy ; d) Requirement for vasopressors; e)and/or Intubation/Ventilation; 3) Major bleeding per ISTH; 4) Recurrent PE (confirmed by imaging); and/or 5) Surgical correction of device related complication. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: From Baseline up to Day 30

For Participants of UK Sites:Change in EuroQual - 5 Dimensions - 5 Levels (EQ-5D-5L) Score From Day 30 to Day 365

The EQ-5D-5L consists of 2 parts - the descriptive system (Index Score) and the EQ Visual Analogue scale (VAS Score). The EQ-5D-5L descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression) and each dimension has 5 levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Each one digit number expressing the level selected for each dimension is combined into a 5-digit number describing the respondent's heath state. These 5-digit numbers are converted into an index value, where 1 represents full health and 0 is equivalent to death. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale with 100 being the best health imaginable and 0 being the worst health imaginable. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: Day 30, Day 365

For Participants of UK Sites: Time From Hospital Admission to Diagnosis of PE

Duration of time between hospital admission and the diagnosis of pulmonary embolism (PE) measured in hours for UK participants.Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: From Baseline through Day 3

For Participants of UK Sites: Time From Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for PE

Duration of time between Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for pulmonary embolism (PE) measured in hours for UK Participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: From Baseline through Day 3

For Participants of UK Sites: Time in Each Level of Care (Level 0 and 1; Level 2; and/or Level 3) Through Discharge

Levels are defined according to National Framework Document: Level 0 - normal acute ward care (patients whose needs can be met through normal ward care in an acute hospital), Level 1 - acute ward care, with additional advice and support from the critical care team (Patients at risk of their condition deteriorating, or those recently relocated from higher levels of care, whose needs can be met on an acute ward with additional advice from a critical care team), Level 2 - more detailed observation or intervention (requiring more detailed observation or intervention including support for a single failing organ system or post-operative care and those 'stepping down' from higher levels of care) and Level 3 - advanced respiratory support alone, or basic respiratory support together with support of at least two organ systems (includes all complex patients requiring support for multi-organ failure). Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: From Baseline up to Hospital Discharge

Healthcare Resource Utilization: Team Managing the Participant During Hospitalization - Number of Healthcare Professional (HCP) Specialties Involved. (UK Participants Only)

Number of Healthcare Professional (HCP) Specialists involved with care of participant during hospitalization of UK participants.Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: From Baseline up to Day 365

Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12month Follow-up. (UK Participants Only)

Number of Healthcare Professional (HCP) Specialists involved with care of participant for Venous Thromboembolism (VTE) after hospitalization through 365 days for UK participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: From Day 30 up to Day 365

Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12 Month Follow-up. (UK Participants Only)

Number of Healthcare Professional (HCP) Specialists involved with care of participant for Venous Thromboembolism (VTE) after hospitalization through 365 days for UK participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: From Day 30 up to Day 365

Healthcare Resource Utilization: Number of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)

Number of Hospital Re-Admissions after hospitalization and during 12 month follow-up for UK Participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: From Day 30 up to Day 365

Healthcare Resource Utilization: Duration of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only)

Duration of Hospital Re-Admissions after hospitalization and during 12 month follow-up for UK Participants. Due to changes in the protocol, there were no subjects enrolled in the UK in Treatment Arm 4.

Time frame: From Day 30 through Day 365