Pulmonary Embolism, Pulmonary Thromboembolism
Conditions
Keywords
PE, pulmonary embolism, thrombectomy, FlowTriever, CDT, Catheter-Directed Thrombolysis
Brief summary
A prospective, multicenter, randomized controlled trial of the FlowTriever System compared to Catheter-Directed Thrombolysis (CDT) for use in the treatment of acute pulmonary embolism. The trial includes a non-randomized cohort of subjects with an absolute contraindication to thrombolysis.
Interventions
Catheter-Directed Thrombolysis for pulmonary embolism (any commercially available CDT system)
DEVICEFlowTriever System
Mechanical thrombectomy for pulmonary embolism
Sponsors
Inari Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must meet each of the following criteria to be included in the study: * Age ≥ 18 years * Echo, computed tomographic pulmonary angiography (CTPA), or pulmonary angiographic evidence of any proximal filling defect in at least one main or lobar pulmonary artery * Including ALL of the following: Clinical signs and symptoms consistent with acute PE, or PESI class III-V, or sPESI ≥1; AND Hemodynamically stable AND; RV dysfunction on echocardiography or CT; AND Any one or more of the following present at the time of diagnosis: Elevated cardiac troponin levels; History of heart failure; History of chronic lung disease; Heart rate ≥110 beats per minute; SBP \<100mmHg; Respiratory rate ≥30 breaths per minute; O2 saturation \<90%; Syncope related to PE; Elevated Lactate * Intervention planned to begin within 72 hours of the later of either: confirmed PE diagnosis; OR if transferring from another hospital, arrival at the treating hospital * Symptom onset within 14 days of confirmed PE diagnosis
Exclusion criteria
Subjects will be excluded from the study for any of the following criteria: * Unable to anticoagulate with heparin, enoxaparin or other parenteral antithrombin * Index presentation with hemodynamic instability that are part of the high-risk PE definition in the ESC Guidelines 2019, including ANY of the following: cardiac arrest; OR systolic BP \< 90 mmHg or vasopressors required to achieve a BP ≥90 mmHg despite adequate filling status, AND end-organ hypoperfusion; OR systolic BP \< 90 mmHg or systolic BP drop ≥40 mmHg, lasting longer than 15 min and not caused by new-onset arrhythmia, hypovolemia, or sepsis * Known sensitivity to radiographic contrast agents that, in the Investigator's opinion, cannot be adequately pre-treated * Imaging evidence or other evidence that suggests, in the opinion of the Investigator, the patient is not appropriate for catheter-based intervention (e.g. inability to navigate to target location, clot limited to segmental/subsegmental distribution, predominately chronic clot) * Patient has right heart clot in transit identified at baseline screening * Life expectancy \< 30 days (e.g. stage 4 cancer or severe COVID-19 infection), as determined by the Investigator * Current participation in another drug or device study that, in the Investigator's opinion, would interfere with participation in this study * Current or history of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic thromboembolic disease (CTED) diagnosis, per ESC 2019 guidelines * Invasive systolic PA pressure ≥70 mmHg prior to study device entering the body * Administration of bolus or drip/infusion thrombolytic therapy or mechanical thrombectomy for the index PE event within 48 hours prior to enrollment * Ventricular arrhythmias refractory to treatment at the time of enrollment * Known to have heparin-induced thrombocytopenia (HIT) * Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments). This includes a contraindication to use of FlowTriever or CDT System (for example, EKOS System) per local approved labeling * Subject has previously completed or withdrawn from this study * Patient unwilling or unable to conduct the follow up visits per protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Endpoint: Composite Clinical Endpoint Constructed as a 5-Component Win Ratio | Hospital discharge or at 7 days after the index procedure, whichever is sooner | The primary endpoint is a composite constructed as a hierarchical win ratio of the following 5 components: 1. All-cause mortality, or 2. Intracranial hemorrhage (ICH), or 3. Major bleeding per ISTH definition, or 4. Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy, or 5. ICU admission and ICU length-of-stay during the index hospitalization and following the index procedure. A win ratio larger than 1 indicates that patients who receive treatment with FlowTriever are more likely to have better outcomes as compared to subjects treated with CDT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | Hospital discharge or at 7 days after the index procedure, whichever is sooner | — |
| Intracranial Hemorrhage (ICH) | Hospital discharge or at 7 days after the index procedure, whichever is sooner | — |
| Major Bleeding Per ISTH Definition | Hospital discharge or at 7 days after the index procedure, whichever is sooner | — |
| Clinical Deterioration Defined by Hemodynamic or Respiratory Worsening, and/or Escalation to a Bailout Therapy | Hospital discharge or at 7 days after the index procedure, whichever is sooner | Clinical deterioration is defined as documented objective hemodynamic or respiratory worsening that is new (i.e. not present at the time of enrollment). Bailout therapy is an unplanned escalation of therapeutic measures, taken when the patient's condition has not improved or is not improving according to expectations. |
| ICU Admission During the Index Hospitalization and Following the Index Procedure | Hospital discharge or at 7 days after the index procedure, whichever is sooner | — |
| ICU Length of Stay During the Index Hospitalization and Following the Index Procedure Among Subjects With ICU Admission. | Hospital discharge or at 7 days after the index procedure, whichever is sooner | — |
| All Cause Mortality | 30 days from index procedure | — |
| All-cause and PE-related Readmissions | 30 days from index procedure | — |
| Device-related Serious Adverse Events | Through the 30 day visit | Device-related SAEs included those adjudicated by the CEC to be related to the interventional device. |
| Composite Clinical Endpoint Constructed as a 4-Component Win Ratio | Hospital discharge or at 7 days after the index procedure, whichever is sooner | This secondary endpoint is a composite constructed as a hierarchical win ratio of the following 4 components: * All-cause mortality, or * Intracranial hemorrhage (ICH), or * Major bleeding per ISTH definition, or * Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy A win ratio larger than 1 indicates that patients who receive treatment with FlowTriever are more likely to have better outcomes as compared to subjects treated with CDT. |
| Clinically Relevant Non-Major (CRNM) and Minor Bleeding Events | Hospital discharge or at 7 days after the index procedure, whichever is sooner | — |
| Change in Right-ventricular/Left-ventricular (RV/LV) Ratio, as Measured by Echocardiography or CT | Baseline to 24 hour visit | Assessments of change were made using the same imaging modality at baseline and at the 24-hour visit. |
| Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | At 24 hour visit | The mMRC score is reported on a 0-4 scale with lower scores representing less dyspnea. |
| Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | At 30 day visit | The mMRC score is reported on a 0-4 scale with lower scores representing less dyspnea. |
| Length of Total Hospital Stay | Through 30 days post-procedure | — |
| Length of Post-index-procedure Hospital Stay | Through 30 days post-procedure | — |
| Pulmonary Embolism Quality of Life (PEmb-QOL) Score at 30 Day Visit | At 30 day visit | The Pulmonary Embolism Quality of Life (PEmb-QOL) questionnaire is used to assess the quality of life in patients with pulmonary embolism (PE). It is a disease-specific tool designed to evaluate the impact of PE on various aspects of a patient's life, including daily activities, work, social life, and emotional well-being, and is reported on a 0-100 scale with lower scores representing better quality of life. |
| EQ-5D-5L Quality of Life Score at 30 Day Visit | At 30 day visit | Each of the five dimensions comprising the EQ-5D-5L descriptive system (mobility, self-care, usual activates, pain/discomfort, anxiety/depression) are graded from 1 (no problems) to 5 (extreme problems). A descriptive health state is defined by combining each level for 5 dimensions into a 5-digit code (e.g., 12345) which is then mapped to the health state index score based on a country-specific value set. Health state index scores range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health). |
| Drug-related Serious Adverse Events | Through the 30 day visit | Drug-related SAEs included those adjudicated by the CEC to be related to anticoagulation and/or thrombolytics medication. |
Countries
Germany, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm Mechanical thrombectomy for pulmonary embolism using the FlowTriever System. | 274 |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm Catheter-Directed Thrombolysis for pulmonary embolism (any commercially available CDT system). | 276 |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort Mechanical thrombectomy for pulmonary embolism using the FlowTriever System. | 142 |
| Total | 692 |
Baseline characteristics
| Characteristic | Total | Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Randomized Controlled Trial Cohort - FlowTriever Arm | Non-Randomized Absolute Contraindication to Thrombolytics Cohort |
|---|---|---|---|---|
| Absolute contraindication to thrombolytics Active internal bleeding, excluding menses | 12 Participants | 0 Participants | 0 Participants | 12 Participants |
| Absolute contraindication to thrombolytics Any other condition on the product label for use by local standard and investigator discretion | 62 Participants | 0 Participants | 0 Participants | 62 Participants |
| Absolute contraindication to thrombolytics Aortic dissection | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Absolute contraindication to thrombolytics Bleeding diathesis | 10 Participants | 0 Participants | 0 Participants | 10 Participants |
| Absolute contraindication to thrombolytics History of hemorrhagic stroke or stroke of unknown origin | 10 Participants | 0 Participants | 0 Participants | 10 Participants |
| Absolute contraindication to thrombolytics Ischemic stroke in the previous 6 months | 4 Participants | 0 Participants | 0 Participants | 4 Participants |
| Absolute contraindication to thrombolytics Presence of intracranial conditions such as neoplasms, arteriovenous malformations, or aneurysms | 24 Participants | 0 Participants | 0 Participants | 24 Participants |
| Absolute contraindication to thrombolytics Recent (3 months) intracranial or intraspinal surgery or serious head trauma | 32 Participants | 0 Participants | 0 Participants | 32 Participants |
| Absolute contraindication to thrombolytics Severe uncontrolled hypertension | 5 Participants | 0 Participants | 0 Participants | 5 Participants |
| Absolute contraindication to thrombolytics Total | 142 Participants | 0 Participants | 0 Participants | 142 Participants |
| Active bleeding preprocedure | 14 Participants | 2 Participants | 0 Participants | 12 Participants |
| Active cancer | 69 Participants | 17 Participants | 13 Participants | 39 Participants |
| Age, Continuous | 62.8 years STANDARD_DEVIATION 14 | 61.2 years STANDARD_DEVIATION 14.8 | 63.7 years STANDARD_DEVIATION 13 | 64.3 years STANDARD_DEVIATION 13.9 |
| Anemia | 95 Participants | 27 Participants | 21 Participants | 47 Participants |
| Body Mass Index | 34.7 kg/m^2 STANDARD_DEVIATION 8.7 | 36.3 kg/m^2 STANDARD_DEVIATION 9.4 | 34.5 kg/m^2 STANDARD_DEVIATION 8.6 | 32.0 kg/m^2 STANDARD_DEVIATION 6.7 |
| Concomitant deep vein thrombosis | 436 Participants | 168 Participants | 178 Participants | 90 Participants |
| Diastolic blood pressure at diagnosis, mmHg | 83.2 mmHg STANDARD_DEVIATION 14.8 | 84.1 mmHg STANDARD_DEVIATION 14.7 | 83.8 mmHg STANDARD_DEVIATION 14.7 | 80.0 mmHg STANDARD_DEVIATION 14.6 |
| Duration of symptoms, days | 3.1 days STANDARD_DEVIATION 3 | 3.5 days STANDARD_DEVIATION 3.3 | 2.9 days STANDARD_DEVIATION 2.8 | 2.8 days STANDARD_DEVIATION 2.8 |
| Elevated cardiac troponin levels | 649 Participants | 265 Participants | 256 Participants | 128 Participants |
| Heart rate, bpm | 109.3 beats per minute STANDARD_DEVIATION 18.5 | 111.6 beats per minute STANDARD_DEVIATION 20.2 | 107.2 beats per minute STANDARD_DEVIATION 17.1 | 108.9 beats per minute STANDARD_DEVIATION 17.2 |
| History of bleeding | 45 Participants | 9 Participants | 5 Participants | 31 Participants |
| History of cancer | 163 Participants | 56 Participants | 56 Participants | 51 Participants |
| History of pulmonary hypertension | 18 Participants | 5 Participants | 6 Participants | 7 Participants |
| History of renal disease | 90 Participants | 33 Participants | 28 Participants | 29 Participants |
| Intermediate risk PE Intermediate-high-risk PE | 649 Participants | 265 Participants | 256 Participants | 128 Participants |
| Intermediate risk PE Intermediate-low-risk PE | 43 Participants | 11 Participants | 18 Participants | 14 Participants |
| mMRC dyspnea score Score 0 - Dyspnea only with strenuous exercise | 37 Participants | 12 Participants | 16 Participants | 9 Participants |
| mMRC dyspnea score Score 1 - Dyspnea when hurrying or walking up a slight hill | 45 Participants | 17 Participants | 23 Participants | 5 Participants |
| mMRC dyspnea score Score 2 - Walks slower than people of same age due to dyspnea or has to stop for breath when walking | 89 Participants | 39 Participants | 37 Participants | 13 Participants |
| mMRC dyspnea score Score 3 - Stops for breath after walking 100 yards (91 m) or after a few minutes | 202 Participants | 79 Participants | 87 Participants | 36 Participants |
| mMRC dyspnea score Score 4 - Too dyspneic to leave house or breathless when dressing | 309 Participants | 126 Participants | 108 Participants | 75 Participants |
| Modified Borg dyspnea score | 3.36 units on a scale STANDARD_DEVIATION 2.69 | 3.32 units on a scale STANDARD_DEVIATION 2.58 | 3.12 units on a scale STANDARD_DEVIATION 2.63 | 3.93 units on a scale STANDARD_DEVIATION 2.96 |
| Most central PE location at screening Lobar | 59 Participants | 24 Participants | 27 Participants | 8 Participants |
| Most central PE location at screening Main pulmonary artery | 362 Participants | 143 Participants | 143 Participants | 76 Participants |
| Most central PE location at screening Saddle | 271 Participants | 109 Participants | 104 Participants | 58 Participants |
| mPAP, mmHg | 30.4 mmHg STANDARD_DEVIATION 7.4 | 31.1 mmHg STANDARD_DEVIATION 7.2 | 30.0 mmHg STANDARD_DEVIATION 7.6 | 29.7 mmHg STANDARD_DEVIATION 7.5 |
| NYHA classification Class III - Marked limitation of physical activity | 307 Participants | 127 Participants | 122 Participants | 58 Participants |
| NYHA classification Class II - Slight limitation of physical activity | 116 Participants | 51 Participants | 54 Participants | 11 Participants |
| NYHA classification Class I - No limitation of physical activity | 58 Participants | 19 Participants | 26 Participants | 13 Participants |
| NYHA classification Class IV - Unable to carry on any physical activity without discomfort | 203 Participants | 76 Participants | 70 Participants | 57 Participants |
| Parenteral anticoagulation use at baseline Another parenteral agent | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Parenteral anticoagulation use at baseline None | 28 Participants | 8 Participants | 13 Participants | 7 Participants |
| Parenteral anticoagulation use at baseline UFH and/or LMWH: LMWH | 59 Participants | 24 Participants | 25 Participants | 10 Participants |
| Parenteral anticoagulation use at baseline UFH and/or LMWH: Total | 663 Participants | 267 Participants | 261 Participants | 135 Participants |
| Parenteral anticoagulation use at baseline UFH and/or LMWH: UFH | 577 Participants | 236 Participants | 221 Participants | 120 Participants |
| Parenteral anticoagulation use at baseline UFH and/or LMWH: UFH and LMWH | 27 Participants | 7 Participants | 15 Participants | 5 Participants |
| Prior cerebrovascular accident | 32 Participants | 8 Participants | 7 Participants | 17 Participants |
| Prior deep vein thrombosis | 143 Participants | 58 Participants | 60 Participants | 25 Participants |
| Prior pulmonary embolism | 84 Participants | 31 Participants | 41 Participants | 12 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 147 Participants | 56 Participants | 67 Participants | 24 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 61 Participants | 27 Participants | 13 Participants | 21 Participants |
| Race/Ethnicity, Customized Other/multiple | 14 Participants | 7 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Unavailable | 57 Participants | 17 Participants | 20 Participants | 20 Participants |
| Race/Ethnicity, Customized White | 468 Participants | 193 Participants | 184 Participants | 91 Participants |
| Recent surgery (within 3 weeks) | 82 Participants | 12 Participants | 22 Participants | 48 Participants |
| Recent trauma (within 3 weeks) | 33 Participants | 7 Participants | 8 Participants | 18 Participants |
| Relative contraindication to thrombolytics Anemia (hemoglobin <10 g/dL) | 8 Participants | 5 Participants | 3 Participants | 0 Participants |
| Relative contraindication to thrombolytics Oral anticoagulation, except for aspirin | 7 Participants | 3 Participants | 4 Participants | 0 Participants |
| Relative contraindication to thrombolytics Refractory hypertension (SBP >180 mmHg or DBP >110 mmHg on two confirmed measurements | 3 Participants | 2 Participants | 1 Participants | 0 Participants |
| Relative contraindication to thrombolytics Therapeutic LMWH within 24 hours | 6 Participants | 2 Participants | 4 Participants | 0 Participants |
| Relative contraindication to thrombolytics Total | 23 Participants | 11 Participants | 12 Participants | 0 Participants |
| Renal dysfunction (CrCL 30-60 mL/min) | 121 Participants | 45 Participants | 43 Participants | 33 Participants |
| Respiratory rate, rpm | 22.5 respirations per minute STANDARD_DEVIATION 6.4 | 22.4 respirations per minute STANDARD_DEVIATION 5.9 | 22.2 respirations per minute STANDARD_DEVIATION 6.7 | 23.1 respirations per minute STANDARD_DEVIATION 6.7 |
| Right bundle branch block | 97 Participants | 36 Participants | 39 Participants | 22 Participants |
| RV function on echocardiogram Mildly reduced | 27 Participants | 11 Participants | 13 Participants | 3 Participants |
| RV function on echocardiogram Moderately reduced | 102 Participants | 41 Participants | 42 Participants | 19 Participants |
| RV function on echocardiogram Normal | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| RV function on echocardiogram Severely reduced | 297 Participants | 119 Participants | 122 Participants | 56 Participants |
| RV/LV ratio (CTPA or echocardiogram) | 1.29 ratio STANDARD_DEVIATION 0.28 | 1.31 ratio STANDARD_DEVIATION 0.27 | 1.27 ratio STANDARD_DEVIATION 0.26 | 1.31 ratio STANDARD_DEVIATION 0.33 |
| Sex: Female, Male Female | 323 Participants | 134 Participants | 125 Participants | 64 Participants |
| Sex: Female, Male Male | 369 Participants | 142 Participants | 149 Participants | 78 Participants |
| sPESI score Score =0 | 147 Participants | 63 Participants | 70 Participants | 14 Participants |
| sPESI score Score >=1 | 544 Participants | 213 Participants | 203 Participants | 128 Participants |
| sPESI score | 1.4 units on a scale STANDARD_DEVIATION 1.1 | 1.3 units on a scale STANDARD_DEVIATION 1.1 | 1.3 units on a scale STANDARD_DEVIATION 1.1 | 1.7 units on a scale STANDARD_DEVIATION 1.1 |
| Systolic blood pressure at diagnosis, mmHg | 132.0 mmHg STANDARD_DEVIATION 22.5 | 132.1 mmHg STANDARD_DEVIATION 21.7 | 134.0 mmHg STANDARD_DEVIATION 22.4 | 127.7 mmHg STANDARD_DEVIATION 23.7 |
| Time from study hospital presentation to treatment catheter insertion, hours | 26.6 hours STANDARD_DEVIATION 33.4 | 24.9 hours STANDARD_DEVIATION 19.7 | 22.3 hours STANDARD_DEVIATION 17.7 | 38.3 hours STANDARD_DEVIATION 62.8 |
| VTE-BLEED score Score <2 | 466 Participants | 199 Participants | 206 Participants | 61 Participants |
| VTE-BLEED score Score >=2 | 226 Participants | 77 Participants | 68 Participants | 81 Participants |
| VTE-BLEED score | 1.8 units on a scale STANDARD_DEVIATION 1.49 | 1.56 units on a scale STANDARD_DEVIATION 1.31 | 1.55 units on a scale STANDARD_DEVIATION 1.3 | 2.77 units on a scale STANDARD_DEVIATION 1.78 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 274 | 2 / 276 | 6 / 142 |
| other Total, other adverse events | 23 / 274 | 18 / 276 | 13 / 142 |
| serious Total, serious adverse events | 43 / 274 | 47 / 276 | 35 / 142 |
Outcome results
Primary
Primary Endpoint: Composite Clinical Endpoint Constructed as a 5-Component Win Ratio
The primary endpoint is a composite constructed as a hierarchical win ratio of the following 5 components: 1. All-cause mortality, or 2. Intracranial hemorrhage (ICH), or 3. Major bleeding per ISTH definition, or 4. Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy, or 5. ICU admission and ICU length-of-stay during the index hospitalization and following the index procedure. A win ratio larger than 1 indicates that patients who receive treatment with FlowTriever are more likely to have better outcomes as compared to subjects treated with CDT.
Time frame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Population: Enrolled subjects in the Randomized Controlled Trial Cohort - FlowTriever Arm and Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm were assessed for this Outcome Measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Primary Endpoint: Composite Clinical Endpoint Constructed as a 5-Component Win Ratio | 52693 Number of Wins for the group |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Primary Endpoint: Composite Clinical Endpoint Constructed as a 5-Component Win Ratio | 10509 Number of Wins for the group |
95% CI: [3.68, 6.97]
Secondary
All-cause and PE-related Readmissions
Time frame: 30 days from index procedure
Population: All enrolled subjects with available outcome
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | All-cause and PE-related Readmissions | All-cause readmission | 8 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | All-cause and PE-related Readmissions | PE-related readmission | 0 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | All-cause and PE-related Readmissions | All-cause readmission | 19 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | All-cause and PE-related Readmissions | PE-related readmission | 2 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | All-cause and PE-related Readmissions | All-cause readmission | 13 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | All-cause and PE-related Readmissions | PE-related readmission | 1 Participants |
Secondary
All-cause Mortality
Time frame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Population: All enrolled subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | All-cause Mortality | 0 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | All-cause Mortality | 1 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | All-cause Mortality | 0 Participants |
Secondary
All Cause Mortality
Time frame: 30 days from index procedure
Population: All enrolled subjects with available outcome
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | All Cause Mortality | 1 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | All Cause Mortality | 2 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | All Cause Mortality | 5 Participants |
Secondary
Change in Right-ventricular/Left-ventricular (RV/LV) Ratio, as Measured by Echocardiography or CT
Assessments of change were made using the same imaging modality at baseline and at the 24-hour visit.
Time frame: Baseline to 24 hour visit
Population: All enrolled subjects with available outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Change in Right-ventricular/Left-ventricular (RV/LV) Ratio, as Measured by Echocardiography or CT | -0.32 ratio | Standard Deviation 0.24 |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Change in Right-ventricular/Left-ventricular (RV/LV) Ratio, as Measured by Echocardiography or CT | -0.30 ratio | Standard Deviation 0.26 |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Change in Right-ventricular/Left-ventricular (RV/LV) Ratio, as Measured by Echocardiography or CT | -0.38 ratio | Standard Deviation 0.29 |
Secondary
Clinical Deterioration Defined by Hemodynamic or Respiratory Worsening, and/or Escalation to a Bailout Therapy
Clinical deterioration is defined as documented objective hemodynamic or respiratory worsening that is new (i.e. not present at the time of enrollment). Bailout therapy is an unplanned escalation of therapeutic measures, taken when the patient's condition has not improved or is not improving according to expectations.
Time frame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Population: All enrolled subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Clinical Deterioration Defined by Hemodynamic or Respiratory Worsening, and/or Escalation to a Bailout Therapy | 5 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Clinical Deterioration Defined by Hemodynamic or Respiratory Worsening, and/or Escalation to a Bailout Therapy | 15 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Clinical Deterioration Defined by Hemodynamic or Respiratory Worsening, and/or Escalation to a Bailout Therapy | 5 Participants |
Secondary
Clinically Relevant Non-Major (CRNM) and Minor Bleeding Events
Time frame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Population: All enrolled subjects with available outcome
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Clinically Relevant Non-Major (CRNM) and Minor Bleeding Events | Clinically relevant non-major (CRNM) bleeding events | 7 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | Clinically Relevant Non-Major (CRNM) and Minor Bleeding Events | Minor bleeding events | 6 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Clinically Relevant Non-Major (CRNM) and Minor Bleeding Events | Clinically relevant non-major (CRNM) bleeding events | 9 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Clinically Relevant Non-Major (CRNM) and Minor Bleeding Events | Minor bleeding events | 1 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Clinically Relevant Non-Major (CRNM) and Minor Bleeding Events | Clinically relevant non-major (CRNM) bleeding events | 6 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Clinically Relevant Non-Major (CRNM) and Minor Bleeding Events | Minor bleeding events | 0 Participants |
Secondary
Composite Clinical Endpoint Constructed as a 4-Component Win Ratio
This secondary endpoint is a composite constructed as a hierarchical win ratio of the following 4 components: * All-cause mortality, or * Intracranial hemorrhage (ICH), or * Major bleeding per ISTH definition, or * Clinical deterioration defined by hemodynamic or respiratory worsening, and/or escalation to a bailout therapy A win ratio larger than 1 indicates that patients who receive treatment with FlowTriever are more likely to have better outcomes as compared to subjects treated with CDT.
Time frame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Population: Enrolled subjects in the Randomized Controlled Trial Cohort - FlowTriever Arm and Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm were assessed for this Outcome Measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Composite Clinical Endpoint Constructed as a 4-Component Win Ratio | 7925 Number of Wins for the group |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Composite Clinical Endpoint Constructed as a 4-Component Win Ratio | 5912 Number of Wins for the group |
95% CI: [0.78, 2.35]
Secondary
Device-related Serious Adverse Events
Device-related SAEs included those adjudicated by the CEC to be related to the interventional device.
Time frame: Through the 30 day visit
Population: All enrolled subjects with available outcome
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Device-related Serious Adverse Events | 19 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Device-related Serious Adverse Events | 12 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Device-related Serious Adverse Events | 9 Participants |
Secondary
Drug-related Serious Adverse Events
Drug-related SAEs included those adjudicated by the CEC to be related to anticoagulation and/or thrombolytics medication.
Time frame: Through the 30 day visit
Population: All enrolled subjects with available outcome
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Drug-related Serious Adverse Events | 31 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Drug-related Serious Adverse Events | 28 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Drug-related Serious Adverse Events | 18 Participants |
Secondary
EQ-5D-5L Quality of Life Score at 30 Day Visit
Each of the five dimensions comprising the EQ-5D-5L descriptive system (mobility, self-care, usual activates, pain/discomfort, anxiety/depression) are graded from 1 (no problems) to 5 (extreme problems). A descriptive health state is defined by combining each level for 5 dimensions into a 5-digit code (e.g., 12345) which is then mapped to the health state index score based on a country-specific value set. Health state index scores range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health).
Time frame: At 30 day visit
Population: All enrolled subjects with available outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | EQ-5D-5L Quality of Life Score at 30 Day Visit | 0.829 score on a scale | Standard Deviation 0.218 |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | EQ-5D-5L Quality of Life Score at 30 Day Visit | 0.817 score on a scale | Standard Deviation 0.237 |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | EQ-5D-5L Quality of Life Score at 30 Day Visit | 0.742 score on a scale | Standard Deviation 0.284 |
Secondary
ICU Admission During the Index Hospitalization and Following the Index Procedure
Time frame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Population: All enrolled subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | ICU Admission During the Index Hospitalization and Following the Index Procedure | 114 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | ICU Admission During the Index Hospitalization and Following the Index Procedure | 272 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | ICU Admission During the Index Hospitalization and Following the Index Procedure | 65 Participants |
Secondary
ICU Length of Stay During the Index Hospitalization and Following the Index Procedure Among Subjects With ICU Admission.
Time frame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Population: All enrolled subjects with available outcome
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | ICU Length of Stay During the Index Hospitalization and Following the Index Procedure Among Subjects With ICU Admission. | ICU length of stay 0-24 hours | 61 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | ICU Length of Stay During the Index Hospitalization and Following the Index Procedure Among Subjects With ICU Admission. | ICU length of stay >24 hours | 53 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | ICU Length of Stay During the Index Hospitalization and Following the Index Procedure Among Subjects With ICU Admission. | ICU length of stay 0-24 hours | 94 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | ICU Length of Stay During the Index Hospitalization and Following the Index Procedure Among Subjects With ICU Admission. | ICU length of stay >24 hours | 178 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | ICU Length of Stay During the Index Hospitalization and Following the Index Procedure Among Subjects With ICU Admission. | ICU length of stay 0-24 hours | 30 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | ICU Length of Stay During the Index Hospitalization and Following the Index Procedure Among Subjects With ICU Admission. | ICU length of stay >24 hours | 35 Participants |
Secondary
Intracranial Hemorrhage (ICH)
Time frame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Population: All enrolled subjects with available outcome
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Intracranial Hemorrhage (ICH) | 2 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Intracranial Hemorrhage (ICH) | 1 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Intracranial Hemorrhage (ICH) | 0 Participants |
Secondary
Length of Post-index-procedure Hospital Stay
Time frame: Through 30 days post-procedure
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Length of Post-index-procedure Hospital Stay | 3.2 days | Standard Deviation 2.72 |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Length of Post-index-procedure Hospital Stay | 4.0 days | Standard Deviation 3.71 |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Length of Post-index-procedure Hospital Stay | 5.4 days | Standard Deviation 5.8 |
Secondary
Length of Total Hospital Stay
Time frame: Through 30 days post-procedure
Population: All enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Length of Total Hospital Stay | 4.5 hospital overnights | Standard Deviation 2.8 |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Length of Total Hospital Stay | 5.3 hospital overnights | Standard Deviation 3.9 |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Length of Total Hospital Stay | 7.8 hospital overnights | Standard Deviation 7.4 |
Secondary
Major Bleeding Per ISTH Definition
Time frame: Hospital discharge or at 7 days after the index procedure, whichever is sooner
Population: All enrolled subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Major Bleeding Per ISTH Definition | 19 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Major Bleeding Per ISTH Definition | 19 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Major Bleeding Per ISTH Definition | 10 Participants |
Secondary
Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit
The mMRC score is reported on a 0-4 scale with lower scores representing less dyspnea.
Time frame: At 24 hour visit
Population: All enrolled subjects with available outcome
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 3 - Stops for breath after walking 100 yards (91 m) or after a few minutes | 27 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 2 - Walks slower than people of the same age due to dyspnea or stops for breath when walking | 61 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 0 - Dyspnea only with strenuous exercise | 80 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 1 - Dyspnea when hurrying or walking up a slight hill | 83 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 4 - Too dyspneic to leave house or breathless when dressing | 8 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 2 - Walks slower than people of the same age due to dyspnea or stops for breath when walking | 53 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 0 - Dyspnea only with strenuous exercise | 77 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 1 - Dyspnea when hurrying or walking up a slight hill | 54 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 3 - Stops for breath after walking 100 yards (91 m) or after a few minutes | 44 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 4 - Too dyspneic to leave house or breathless when dressing | 22 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 4 - Too dyspneic to leave house or breathless when dressing | 5 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 3 - Stops for breath after walking 100 yards (91 m) or after a few minutes | 21 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 0 - Dyspnea only with strenuous exercise | 40 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 2 - Walks slower than people of the same age due to dyspnea or stops for breath when walking | 29 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 24 Hour Visit | Score 1 - Dyspnea when hurrying or walking up a slight hill | 35 Participants |
Secondary
Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit
The mMRC score is reported on a 0-4 scale with lower scores representing less dyspnea.
Time frame: At 30 day visit
Population: All enrolled subjects with available outcome
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 3 - Stops for breath after walking 100 yards (91 m) or after a few minutes | 14 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 2 - Walks slower than people of the same age due to dyspnea or stops for breath when walking | 28 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 0 - Dyspnea only with strenuous exercise | 137 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 1 - Dyspnea when hurrying or walking up a slight hill | 74 Participants |
| Randomized Controlled Trial Cohort - FlowTriever Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 4 - Too dyspneic to leave house or breathless when dressing | 5 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 2 - Walks slower than people of the same age due to dyspnea or stops for breath when walking | 27 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 0 - Dyspnea only with strenuous exercise | 138 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 1 - Dyspnea when hurrying or walking up a slight hill | 63 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 3 - Stops for breath after walking 100 yards (91 m) or after a few minutes | 23 Participants |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 4 - Too dyspneic to leave house or breathless when dressing | 3 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 4 - Too dyspneic to leave house or breathless when dressing | 5 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 3 - Stops for breath after walking 100 yards (91 m) or after a few minutes | 6 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 0 - Dyspnea only with strenuous exercise | 60 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 2 - Walks slower than people of the same age due to dyspnea or stops for breath when walking | 17 Participants |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Modified Medical Research Council (mMRC) Dyspnea Score at 30 Day Visit | Score 1 - Dyspnea when hurrying or walking up a slight hill | 33 Participants |
Secondary
Pulmonary Embolism Quality of Life (PEmb-QOL) Score at 30 Day Visit
The Pulmonary Embolism Quality of Life (PEmb-QOL) questionnaire is used to assess the quality of life in patients with pulmonary embolism (PE). It is a disease-specific tool designed to evaluate the impact of PE on various aspects of a patient's life, including daily activities, work, social life, and emotional well-being, and is reported on a 0-100 scale with lower scores representing better quality of life.
Time frame: At 30 day visit
Population: All enrolled subjects with available outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Controlled Trial Cohort - FlowTriever Arm | Pulmonary Embolism Quality of Life (PEmb-QOL) Score at 30 Day Visit | 19.33 score on a scale | Standard Deviation 18.91 |
| Randomized Controlled Trial Cohort - Catheter-Directed Thrombolysis Arm | Pulmonary Embolism Quality of Life (PEmb-QOL) Score at 30 Day Visit | 20.42 score on a scale | Standard Deviation 19.95 |
| Non-Randomized Absolute Contraindication to Thrombolytics Cohort | Pulmonary Embolism Quality of Life (PEmb-QOL) Score at 30 Day Visit | 23.50 score on a scale | Standard Deviation 21.75 |