Trial Outcomes & Findings for Treatment of Chronic Deep Vein Thrombosis (DVT) and Post-Thrombotic Syndrome (PTS) With the EkoSonic® Endovascular System (NCT NCT02159521)

Last Updated: 2021-07-19

Results Overview

Clinical efficacy was evaluated using the Villalta score at Baseline compared to 30 days Post-EkoSonic® study treatment procedure. Villalta scale (post thrombotic syndrome score) is used for the assessment of symptoms and clinical signs. Participants rated the following symptoms for each leg: pain, cramps, heaviness, pruritus, and paresthesia on a scale ranging from 0 (not present/minimal) to 3 (severe). The study coordinator or nurse rated the following clinical signs in participants for each leg: pre-tibial edema, induration of the skin, hyperpigmentation, new venous extasia, redness during calf compression, and pain during calf compression on a scale ranging from 0 (not present/minimal) to 3 (severe). Total score ranged from 0 to 33. Higher scores represent more severe disease.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

81 participants

Primary outcome timeframe

Baseline (within 30 days of treatment), Day 30

Results posted on

2021-07-19

Participant Flow

Unit of analysis: Limbs

Participant milestones

Participant milestones
Measure	EkoSonic® Endovascular System Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 milligrams/hour (mg/hr) was delivered to the participants with chronic lower extremity venous obstruction after deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS), through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Overall Study STARTED	81 85
Overall Study Received EkoSonic® Treatment	78 82
Overall Study COMPLETED	63 67
Overall Study NOT COMPLETED	18 18

Reasons for withdrawal

Reasons for withdrawal
Measure	EkoSonic® Endovascular System Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 milligrams/hour (mg/hr) was delivered to the participants with chronic lower extremity venous obstruction after deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS), through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Overall Study Enrolled but not treated	3
Overall Study Withdrawal by Subject	7
Overall Study Lost to Follow-up	6
Overall Study Death	1
Overall Study Other than specified	1

Baseline Characteristics

Treatment of Chronic Deep Vein Thrombosis (DVT) and Post-Thrombotic Syndrome (PTS) With the EkoSonic® Endovascular System

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EkoSonic® Endovascular System n=78 Participants Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Age, Continuous	54.6 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian, not of Hispanic origin	58 Participants n=5 Participants
Race/Ethnicity, Customized African American, not of Hispanic origin	12 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 Participants n=5 Participants
Race/Ethnicity, Customized Asian or Pacific Islander	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (within 30 days of treatment), Day 30

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated. Here, 'Number analyzed' signifies number of limbs analyzed at specified timepoints.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=82 Limbs Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Change From Baseline in Villalta Score at Day 30 Post-EkoSonic® Study Treatment Procedure Change at Day 30	-5.9 units on a scale Standard Deviation 5.75
Change From Baseline in Villalta Score at Day 30 Post-EkoSonic® Study Treatment Procedure Baseline	15.5 units on a scale Standard Deviation 5.17

PRIMARY outcome

Timeframe: Baseline (within 30 days of treatment), Day 30

Clinical efficacy was evaluated using the Villalta score at Baseline compared to 30 days Post-EkoSonic® study treatment procedure. Limbs with revascularization procedures were considered non-responders. Villalta scale (post thrombotic syndrome score) is used for the assessment of symptoms and clinical signs. Participants rated the following symptoms for each leg: pain, cramps, heaviness, pruritus, and paresthesia on a scale ranging from 0 (not present/minimal) to 3 (severe). The study coordinator or nurse rated the following clinical signs in participants for each leg: pre-tibial edema, induration of the skin, hyperpigmentation, new venous extasia, redness during calf compression, and pain during calf compression on a scale ranging from 0 (not present/minimal) to 3 (severe). Total score ranged from 0 to 33. Higher scores represent more severe disease.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=79 Limbs Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Percentage of Segments of Limbs That Achieved at Least 4-Point Reduction From Baseline in Villalta Score at Day 30	64 percentage of segments Interval 54.0 to 74.0

PRIMARY outcome

Timeframe: Baseline (Within 30 days of treatment), Day 0

Population: ITT population included all enrolled participants for whom EkoSonic® treatment was initiated. Here, 'Overall number of participants analyzed'/'Overall Number of Units Analyzed' signifies the number of participants/units evaluable for this outcome measure and 'Number analyzed' signifies number of limbs/participants analyzed at specified timepoints.

Change in blood flow was calculated by time to washout in the affected segments in the participants. Time to femoral vein (FV) washout and external iliac vein (EIV) washout was reported.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=50 Limbs Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Change From Baseline in Blood Flow (Calculated by Time to Washout in the Affected Segment) at Post-Adjunctive Therapy FV washout: Baseline	4.39 seconds Standard Deviation 2.55
Change From Baseline in Blood Flow (Calculated by Time to Washout in the Affected Segment) at Post-Adjunctive Therapy FV washout: Change at Day 0	-2.17 seconds Standard Deviation 2.24
Change From Baseline in Blood Flow (Calculated by Time to Washout in the Affected Segment) at Post-Adjunctive Therapy EIV washout: Baseline	3.28 seconds Standard Deviation 2.73
Change From Baseline in Blood Flow (Calculated by Time to Washout in the Affected Segment) at Post-Adjunctive Therapy EIV washout: Change at Day 0	-0.96 seconds Standard Deviation 2.99

PRIMARY outcome

Timeframe: From start of study drug infusion up to 72 hours

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.

Major bleeding was defined as: Fatal bleeding; and/or symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome; and/or bleeding causing a fall in hemoglobin of ≥2.0 grams/deciliter (g/dL), or leading to transfusion of ≥2 units of whole blood or red blood cells. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=78 Participants Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Number of Participants With Major Bleeding	1 Participants

SECONDARY outcome

Timeframe: Baseline (Within 30 days of treatment), Day 0

The Ouriel score was designed to provide a more accurate quantitative estimate of the thrombus mass by calculating a volumetric index for all the venous segments. 10 venous segments were considered. Included segments were the inferior vena cava, common iliac veins, external iliac veins, internal iliac veins, common femoral veins, superficial and deep femoral veins, and popliteal veins and segments of the anterior tibial veins, posterior tibial veins, and peroneal veins. A normalized volumetric score was calculated for each segment by combining measurements from computed tomography, ultrasonography, and venography. Partially occluded veins were assigned a score of one-half the score value for the segment. The score varies from 1 for a single calf vein to 26 for the infrarenal inferior vena cava. The maximum score was 63 per limb. Higher score indicated worse disease prognoses.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=71 Limbs Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Change From Baseline in Ouriel Score (Venous Volumetric Index [VVI]) at Post-Adjunctive Therapy Baseline	10.58 units on a scale Standard Deviation 6.25
Change From Baseline in Ouriel Score (Venous Volumetric Index [VVI]) at Post-Adjunctive Therapy Change at Post-EkoSonic® procedure	6.88 units on a scale Standard Deviation 5.69

SECONDARY outcome

Timeframe: Baseline (Within 30 days of treatment), Day 0

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated. Here, 'Number analyzed' signifies number of participants analyzed.

The Ouriel score was designed to provide a more accurate quantitative estimate of the thrombus mass by calculating a volumetric index for all the venous segments. 14 venous segments were considered. Included segments were the inferior vena cava, common iliac veins, external iliac veins, internal iliac veins, common femoral veins, superficial femoral veins, deep femoral veins, and popliteal veins and segments of the anterior tibial veins, posterior tibial veins, and peroneal veins. A normalized volumetric score was calculated for each segment by combining measurements from computed tomography, ultrasonography, and venography. Partially occluded veins were assigned a score of one-half the score value for the segment. The score varies from 1 for a single calf vein to 26 for the infrarenal inferior vena cava. The maximum score was 63 per limb. Higher score indicated worse disease prognoses.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=54 Participants Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Number of Participants With at Least 5-Point Reduction From Baseline in Ouriel Score at Post-Adjunctive Therapy	0 Participants

SECONDARY outcome

Timeframe: Baseline (within 30 days of treatment), Days 90, 180, and 365

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated. Here, 'Number analyzed' signifies number of limbs and the number of participants analyzed at specified timepoints.

Villalta scale (post thrombotic syndrome score) is used for the assessment of symptoms and clinical signs. Participants rated the following symptoms for each leg: pain, cramps, heaviness, pruritus, and paresthesia on a scale ranging from 0 (not present/minimal) to 3 (severe). The study coordinator or nurse rated the following clinical signs in participants for each leg: pre-tibial edema, induration of the skin, hyperpigmentation, new venous extasia, redness during calf compression, and pain during calf compression on a scale ranging from 0 (not present/minimal) to 3 (severe). Total score ranged from 0 to 33. Higher scores represent more severe disease.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=82 Limbs Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Change From Baseline in Villalta Score at Days 90, 180, and 365 Post-EkoSonic® Study Treatment Procedure Baseline	15.5 units on a scale Standard Deviation 5.17
Change From Baseline in Villalta Score at Days 90, 180, and 365 Post-EkoSonic® Study Treatment Procedure Change at Day 90	-6.9 units on a scale Standard Deviation 6.48
Change From Baseline in Villalta Score at Days 90, 180, and 365 Post-EkoSonic® Study Treatment Procedure Change at Day 180	-7.8 units on a scale Standard Deviation 6.09
Change From Baseline in Villalta Score at Days 90, 180, and 365 Post-EkoSonic® Study Treatment Procedure Change at Day 365	-8.2 units on a scale Standard Deviation 6.43

SECONDARY outcome

Timeframe: Baseline (within 30 days of treatment), Days 90, 180, and 365

Limbs with revascularization procedures were considered non-responders. Villalta scale (post thrombotic syndrome score) is used for the assessment of symptoms and clinical signs. Participants rated the following symptoms for each leg: pain, cramps, heaviness, pruritus, and paresthesia on a scale ranging from 0 (not present/minimal) to 3 (severe). The study coordinator or nurse rated the following clinical signs in participants for each leg: pre-tibial edema, induration of the skin, hyperpigmentation, new venous extasia, redness during calf compression, and pain during calf compression on a scale ranging from 0 (not present/minimal) to 3 (severe). Total score ranged from 0 to 33. Higher scores represent more severe disease.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=74 Limbs Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Percentage of Segments of Limbs That Achieved at Least 4-Point Reduction From Baseline in Villalta Score at Days 90, 180, and 365 Day 90	66 percentage of segments Interval 55.0 to 76.0
Percentage of Segments of Limbs That Achieved at Least 4-Point Reduction From Baseline in Villalta Score at Days 90, 180, and 365 Day 180	74 percentage of segments Interval 62.0 to 84.0
Percentage of Segments of Limbs That Achieved at Least 4-Point Reduction From Baseline in Villalta Score at Days 90, 180, and 365 Day 365	74 percentage of segments Interval 62.0 to 84.0

SECONDARY outcome

Timeframe: Day 365

Absence of re-occlusion in following treated veins has been reported: common femoral vein (CFV), common iliac vein (CIV), distal femoral vein (FV), external iliac vein (EIV), popliteal vein, and proximal femoral vein (FV).

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=63 Vein segments Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Percentage of Treated Veins Segments of Limbs With Absence of Re-Occlusion, as Documented by Duplex Imaging EIV	100 percentage of segments
Percentage of Treated Veins Segments of Limbs With Absence of Re-Occlusion, as Documented by Duplex Imaging CFV	100 percentage of segments
Percentage of Treated Veins Segments of Limbs With Absence of Re-Occlusion, as Documented by Duplex Imaging CIV	100 percentage of segments
Percentage of Treated Veins Segments of Limbs With Absence of Re-Occlusion, as Documented by Duplex Imaging Distal FV	100 percentage of segments
Percentage of Treated Veins Segments of Limbs With Absence of Re-Occlusion, as Documented by Duplex Imaging Popliteal Vein	97.9 percentage of segments
Percentage of Treated Veins Segments of Limbs With Absence of Re-Occlusion, as Documented by Duplex Imaging Proximal FV	100 percentage of segments

SECONDARY outcome

Timeframe: Baseline (within 30 days of treatment), Days 30, 90, 180, and 365

SF- 36 investigates the standard of quality of life through a general health assessment. It is a 36-item questionnaire measuring 8 domains (physical functioning \[PF\], role physical \[RP\], bodily pain \[BP\], general health \[GH\], vitality \[VT\], social functioning \[SF\], role emotional \[RE\], and mental health \[MH\]). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. The PCS score summarizes the subscales physical functioning, role-physical, bodily pain, and general health. Total score range for PCS was 0 (lowest level of physical functioning) to 100 (highest level of physical functioning).

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=82 Limbs Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PF Score: Change at Day 90	14.0 units on a scale Standard Deviation 22.87
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PF Score: Change at Day 180	15.1 units on a scale Standard Deviation 24.75
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PF Score: Change at Day 365	13.9 units on a scale Standard Deviation 23.40
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RP Score: Baseline	47.2 units on a scale Standard Deviation 26.84
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RP Score: Change at Day 90	17.6 units on a scale Standard Deviation 23.65
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RP Score: Change at Day 180	19.5 units on a scale Standard Deviation 27.47
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RP Score: Change at Day 365	17.6 units on a scale Standard Deviation 28.42
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 GH Score: Change at Day 365	0.1 units on a scale Standard Deviation 18.10
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 SF Score: Change at Day 90	11.3 units on a scale Standard Deviation 24.40
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 SF Score: Change at Day 365	9.0 units on a scale Standard Deviation 24.06
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RE Score: Change at Day 90	10.6 units on a scale Standard Deviation 28.30
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RE Score: Change at Day 365	3.9 units on a scale Standard Deviation 31.11
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PF Score: Baseline	48.4 units on a scale Standard Deviation 27.75
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PF Score: Change at Day 30	9.5 units on a scale Standard Deviation 21.72
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RP Score: Change at Day 30	7.1 units on a scale Standard Deviation 27.86
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 BP Score: Baseline	46.2 units on a scale Standard Deviation 25.44
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 BP Score: Change at Day 30	6.9 units on a scale Standard Deviation 27.92
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 BP Score: Change at Day 90	14.4 units on a scale Standard Deviation 28.04
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 BP Score: Change at Day 180	15.2 units on a scale Standard Deviation 29.26
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 BP Score: Change at Day 365	16.0 units on a scale Standard Deviation 28.92
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 GH Score: Baseline	58.6 units on a scale Standard Deviation 22.38
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 GH Score: Change at Day 30	1.1 units on a scale Standard Deviation 17.17
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 GH Score: Change at Day 90	3.4 units on a scale Standard Deviation 16.10
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 GH Score: Change at Day 180	0.8 units on a scale Standard Deviation 15.56
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 VT Score: Baseline	50.5 units on a scale Standard Deviation 23.18
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 VT Score: Change at Day 30	2.8 units on a scale Standard Deviation 24.53
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 VT Score: Change at Day 90	8.9 units on a scale Standard Deviation 19.35
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 VT Score: Change at Day 180	6.6 units on a scale Standard Deviation 21.83
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 VT Score: Change at Day 365	5.7 units on a scale Standard Deviation 20.81
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 SF Score: Baseline	65.4 units on a scale Standard Deviation 31.81
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 SF Score: Change at Day 30	2.7 units on a scale Standard Deviation 30.14
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 SF Score: Change at Day 180	9.9 units on a scale Standard Deviation 27.05
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RE Score: Baseline	70.8 units on a scale Standard Deviation 30.77
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RE Score: Change at Day 30	3.8 units on a scale Standard Deviation 33.83
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 RE Score: Change at Day 180	9.9 units on a scale Standard Deviation 27.90
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 MH Score: Baseline	67.5 units on a scale Standard Deviation 21.58
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 MH Score: Change at Day 30	3.4 units on a scale Standard Deviation 17.70
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 MH Score: Change at Day 180	7.2 units on a scale Standard Deviation 19.12
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 MH Score: Change at Day 365	4.5 units on a scale Standard Deviation 20.77
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PCS Score: Baseline	38.6 units on a scale Standard Deviation 9.47
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PCS Score: Change at Day 30	2.8 units on a scale Standard Deviation 7.62
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PCS Score: Change at Day 90	5.1 units on a scale Standard Deviation 8.52
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PCS Score: Change at Day 180	5.4 units on a scale Standard Deviation 9.24
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 PCS Score: Change at Day 365	5.8 units on a scale Standard Deviation 8.80
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Sub-Scale Score and Physical Component Score (PCS) at Days, 30, 90, 180, and 365 MH Score: Change at Day 90	7.7 units on a scale Standard Deviation 16.54

SECONDARY outcome

Timeframe: Baseline (within 30 days of treatment), Days 30, 90, 180, and 365

Status of clinical signs and symptoms of lower limb venous disease was measured by CEAP classification. The CEAP clinical Categories were as follows: C0- no visible or palpable signs of venous disease, C1- telangiectasies or reticular veins, C2- varicose veins, C3- edema, C4a- pigmentation and eczema, C4b- lipodermatosclerosis and atrophie blanche, C5- healed venous ulcer, and C6- active venous ulcer. C0 was of the least clinical concern and C6 was the worst stage. Each clinical class was further characterized by the (clinical stages) presence or absence of symptoms (ache, pain, tightness, skin irritation, heaviness, muscle cramps, as well as other complaints attributable to venous dysfunction): asymptomatic and symptomatic.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=79 Limbs Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Number of Treated Limbs With Shift From Baseline in Clinical Stages (Symptomatic and Asymptomatic) of Clinical, Etiologic, Anatomic, Pathophysiological (CEAP) Classification at Days 30, 90, 180, and 365 Baseline to Day 30 · Symptomatic - Asymptomatic	12 Limbs
Number of Treated Limbs With Shift From Baseline in Clinical Stages (Symptomatic and Asymptomatic) of Clinical, Etiologic, Anatomic, Pathophysiological (CEAP) Classification at Days 30, 90, 180, and 365 Baseline to Day 180 · Symptomatic - Symptomatic	45 Limbs
Number of Treated Limbs With Shift From Baseline in Clinical Stages (Symptomatic and Asymptomatic) of Clinical, Etiologic, Anatomic, Pathophysiological (CEAP) Classification at Days 30, 90, 180, and 365 Baseline to Day 180 · Symptomatic - Asymptomatic	25 Limbs
Number of Treated Limbs With Shift From Baseline in Clinical Stages (Symptomatic and Asymptomatic) of Clinical, Etiologic, Anatomic, Pathophysiological (CEAP) Classification at Days 30, 90, 180, and 365 Baseline to Day 365 · Symptomatic - Symptomatic	40 Limbs
Number of Treated Limbs With Shift From Baseline in Clinical Stages (Symptomatic and Asymptomatic) of Clinical, Etiologic, Anatomic, Pathophysiological (CEAP) Classification at Days 30, 90, 180, and 365 Baseline to Day 30 · Symptomatic - Symptomatic	67 Limbs
Number of Treated Limbs With Shift From Baseline in Clinical Stages (Symptomatic and Asymptomatic) of Clinical, Etiologic, Anatomic, Pathophysiological (CEAP) Classification at Days 30, 90, 180, and 365 Baseline to Day 90 · Symptomatic - Symptomatic	56 Limbs
Number of Treated Limbs With Shift From Baseline in Clinical Stages (Symptomatic and Asymptomatic) of Clinical, Etiologic, Anatomic, Pathophysiological (CEAP) Classification at Days 30, 90, 180, and 365 Baseline to Day 90 · Symptomatic - Asymptomatic	19 Limbs
Number of Treated Limbs With Shift From Baseline in Clinical Stages (Symptomatic and Asymptomatic) of Clinical, Etiologic, Anatomic, Pathophysiological (CEAP) Classification at Days 30, 90, 180, and 365 Baseline to Day 365 · Symptomatic - Asymptomatic	25 Limbs

SECONDARY outcome

Timeframe: Baseline (within 30 days of treatment), Days 30, 90, 180, and 365

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure and 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.

The VEINES-QOL/Sym is a participant-based questionnaire designed for self-completion and measures deep vein thrombosis (DVT) impact on symptoms and quality of life from the participants' perspective. It contains 26 items covering participant DVT: symptoms, limitations in daily activities, and psychological impact. A separate summary score VEINES-QOL ranges from 0 (worst quality of life) to 100 (best quality of life). Higher scores indicated a better quality of life.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=63 Participants Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Change From Baseline in Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) Score At Days 30, 90, 180, and 360 Baseline	61.1 units on a scale Standard Deviation 19.63
Change From Baseline in Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) Score At Days 30, 90, 180, and 360 Change at Day 180	18.9 units on a scale Standard Deviation 16.23
Change From Baseline in Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) Score At Days 30, 90, 180, and 360 Change at Day 365	18.7 units on a scale Standard Deviation 16.27
Change From Baseline in Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) Score At Days 30, 90, 180, and 360 Change at Day 30	10.3 units on a scale Standard Deviation 15.86
Change From Baseline in Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) Score At Days 30, 90, 180, and 360 Change at Day 90	16.3 units on a scale Standard Deviation 17.96

SECONDARY outcome

Timeframe: Baseline (within 30 days of treatment), Days 30, 90, 180, and 365

The VCSS system includes 10 clinical descriptions (pain, varicose veins, venous edema, skin pigmentation, inflammation, induration, number of active ulcers, duration of active ulceration, size of active ulceration, and level of compliance with medical compression therapy), scored from 0 to 3 (total possible score, 30) with 0 = absent, 1 = mild, 2 = moderate and 3 = severe. Total VCSS was the sum of all VCSS assessment scores from categories for a given time point. Total score ranged from 0 (absent) to 30 (severe). Lower values represent a better outcome, that is, a level of pain less than that experienced at baseline.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=82 Limbs Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Change From Baseline in Venous Clinical Severity Score (VCSS) in Study Leg at Days 30, 90, 180, and 365 Baseline	12.0 units on a scale Standard Deviation 5.33
Change From Baseline in Venous Clinical Severity Score (VCSS) in Study Leg at Days 30, 90, 180, and 365 Change at Day 90	-4.5 units on a scale Standard Deviation 4.97
Change From Baseline in Venous Clinical Severity Score (VCSS) in Study Leg at Days 30, 90, 180, and 365 Change at Day 180	-5.2 units on a scale Standard Deviation 4.68
Change From Baseline in Venous Clinical Severity Score (VCSS) in Study Leg at Days 30, 90, 180, and 365 Change at Day 365	-5.7 units on a scale Standard Deviation 4.38
Change From Baseline in Venous Clinical Severity Score (VCSS) in Study Leg at Days 30, 90, 180, and 365 Change at Day 30	-3.8 units on a scale Standard Deviation 4.33

SECONDARY outcome

Timeframe: From the time of the EkoSonic® procedure (Day 0) up to 365 days

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.

Number of participants with PTS-induced admission to an emergency room or unplanned visits to a physician's office or hospitalization, are reported. A participant can have more than one PTS-induced health issue.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=78 Participants Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Number of Participants With PTS-induced Admission to an Emergency Room or Unplanned Visits to a Physician's Office or Hospitalization Total	24 Participants
Number of Participants With PTS-induced Admission to an Emergency Room or Unplanned Visits to a Physician's Office or Hospitalization Emergency Room	13 Participants
Number of Participants With PTS-induced Admission to an Emergency Room or Unplanned Visits to a Physician's Office or Hospitalization Unplanned Physician Office Visit	18 Participants
Number of Participants With PTS-induced Admission to an Emergency Room or Unplanned Visits to a Physician's Office or Hospitalization Hospitalization	8 Participants

SECONDARY outcome

Timeframe: From the time of the EkoSonic® procedure (Day 0) up to 365 days

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.

This Outcome Measure was to measure the time that the participant's initial thrombolytic infusion started to the time the participant was discharged from the hospital.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=78 Participants Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Time From Starting Initial Thrombolytic Infusion to Discharge From the Hospital	2 days Interval 1.0 to 38.0

SECONDARY outcome

Timeframe: From starting the initial thrombolytic infusion (Day 0) through discharge from hospital (up to Day 38)

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.

Symptomatic PE was diagnosed using computed tomography pulmonary angiogram (CTPA), single positron emission computed tomography (SPECT), and ventilation-perfusion (VQ).

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=78 Participants Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Number of Participants Who Had Symptomatic PE During Hospitalization for Study Procedure	0 Participants

SECONDARY outcome

Timeframe: Baseline (within 30 days of treatment) up to Day 365

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.

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

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=78 Participants Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Number of Participants Who Died Due to Any Cause	1 Participants

SECONDARY outcome

Timeframe: Baseline (within 30 days of treatment) up to Day 30

Population: ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A summary of non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure	EkoSonic® Endovascular System n=78 Participants Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Number of Participants Who Had Adverse Events (AEs), Related (to the Study Procedure/Device/Medications) AEs, and Serious Adverse Events (SAEs) Any AEs	34 Participants
Number of Participants Who Had Adverse Events (AEs), Related (to the Study Procedure/Device/Medications) AEs, and Serious Adverse Events (SAEs) Related to Thrombolytic/Angiographic Procedure	15 Participants
Number of Participants Who Had Adverse Events (AEs), Related (to the Study Procedure/Device/Medications) AEs, and Serious Adverse Events (SAEs) Related to EKOS system	3 Participants
Number of Participants Who Had Adverse Events (AEs), Related (to the Study Procedure/Device/Medications) AEs, and Serious Adverse Events (SAEs) Related to Thrombolytic Drug	8 Participants
Number of Participants Who Had Adverse Events (AEs), Related (to the Study Procedure/Device/Medications) AEs, and Serious Adverse Events (SAEs) Related to Anticoagulant Drug	15 Participants
Number of Participants Who Had Adverse Events (AEs), Related (to the Study Procedure/Device/Medications) AEs, and Serious Adverse Events (SAEs) Related to Post-procedure Adjunctive Treatment	3 Participants
Number of Participants Who Had Adverse Events (AEs), Related (to the Study Procedure/Device/Medications) AEs, and Serious Adverse Events (SAEs) SAEs	12 Participants

Adverse Events

EkoSonic® Endovascular System

Serious events: 16 serious events

Other events: 33 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	EkoSonic® Endovascular System n=78 participants at risk Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Blood and lymphatic system disorders Heparin-induced thrombocytopenia	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Cardiac disorders Atrial fibrillation	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Cardiac disorders Cardiac failure congestive	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
General disorders Oedema	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Infections and infestations Osteomyelitis	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Infections and infestations Septic shock	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Investigations Oxygen saturation decreased	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Metabolism and nutrition disorders Lactic acidosis	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Musculoskeletal and connective tissue disorders Joint effusion	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Musculoskeletal and connective tissue disorders Pain in extremity	3.8% 3/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Renal and urinary disorders Haematuria	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Deep vein thrombosis	10.3% 8/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Epistaxis	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Haematoma	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Pulmonary embolism	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Venous occlusion	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.

Other adverse events

Other adverse events
Measure	EkoSonic® Endovascular System n=78 participants at risk Thrombolytic infusion (Alteplase), at an infusion rate of 0.5-1.0 mg/hr was delivered to the participants with chronic lower extremity venous obstruction after DVT and PTS, through EkoSonic® Endovascular System for at least 12 hours and overnight as needed up to a maximum of 48 hrs. The alteplase dose could have been adjusted per investigator discretion, but was not exceeded 1 mg/hr or a total dose of 48 mg.
Vascular disorders Haematoma	2.6% 2/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Infections and infestations Sinusitis	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Gastrointestinal disorders Nausea	7.7% 6/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Injury, poisoning and procedural complications Procedural haemorrhage	6.4% 5/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Skin and subcutaneous tissue disorders Ecchymosis	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Musculoskeletal and connective tissue disorders Back pain	3.8% 3/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Hypertension	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Musculoskeletal and connective tissue disorders Joint effusion	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Deep vein thrombosis	6.4% 5/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Skin and subcutaneous tissue disorders Pruritus	2.6% 2/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Infections and infestations Urinary tract infection	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Musculoskeletal and connective tissue disorders Groin pain	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Nervous system disorders Dizziness	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Respiratory, thoracic and mediastinal disorders Asthma	2.6% 2/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Immune system disorders Drug hypersensitivity	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Skin and subcutaneous tissue disorders Rash	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Renal and urinary disorders Haematuria	2.6% 2/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Musculoskeletal and connective tissue disorders Pain in extremity	3.8% 3/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Cardiac disorders Bradycardia	2.6% 2/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Pelvic venous thrombosis	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Reproductive system and breast disorders Uterine haemorrhage	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Skin and subcutaneous tissue disorders Skin ulcer	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Nervous system disorders Hypoaesthesia	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Injury, poisoning and procedural complications Contusion	2.6% 2/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Psychiatric disorders Anxiety	2.6% 2/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Epistaxis	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
General disorders Injection site haemorrhage	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Blood and lymphatic system disorders Anaemia	2.6% 2/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Vascular disorders Haemorrhage	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Nervous system disorders Migraine	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Renal and urinary disorders Dysuria	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Gastrointestinal disorders Abdominal pain	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Cardiac disorders Ventricular extrasystoles	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Investigations Blood fibrinogen decreased	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Psychiatric disorders Insomnia	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Gastrointestinal disorders Constipation	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.
Injury, poisoning and procedural complications Post procedural haemorrhage	1.3% 1/78 • Baseline (within 30 days of treatment) up to Day 365 ITT population included all enrolled participants for whom the EkoSonic® treatment was initiated.

Additional Information

David Hahn

EKOS Corporation

Phone: 4254153100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60