Pulmonary Embolism Acute
Conditions
Keywords
intermediate-high risk, acute, PE, clot
Brief summary
The primary objective of this trial is to evaluate the safety and efficacy of treatment with anticoagulation alone versus anticoagulation and mechanical aspiration thrombectomy with the Indigo Aspiration System for the treatment of intermediate-high risk acute pulmonary embolism (PE).
Interventions
DRUGAnticoagulation
Anticoagulation with unfractionated heparin (UFH) or low molecular weight heparin (LMWH)
Mechanical aspiration thrombectomy with the Indigo Aspiration System.
Sponsors
Penumbra Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomization will be 1:1 to either anticoagulation alone (AC Group) or anticoagulation plus mechanical aspiration thrombectomy with the Indigo Aspiration System (Indigo Group).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80 years old 2. Clinical signs and symptoms consistent with acute PE with duration of 14 days or less 3. Objectively confirmed acute PE, based on computed tomographic pulmonary angiography (CTPA) imaging showing a filling defect in at least one main or proximal lobar pulmonary artery 4. Classification of intermediate high-risk PE as demonstrated by right ventricular dysfunction with RV/LV ratio ≥1.0 on CTPA and elevated cardiac biomarkers, including cardiac troponin, BNP, and/or NT-pro BNP above the upper limit of normal 5. Jugular or femoral access deemed suitable to accommodate pulmonary artery intervention with the Indigo Aspiration System 6. Informed consent is obtained from either the patient or legally authorized representative (LAR)
Exclusion criteria
1. Administration of thrombolytic agents or glycoprotein IIb/IIIa receptor antagonist within 30 days prior to baseline imaging 2. Hemodynamic instability with any of the following present: 1. Cardiac arrest 2. Obstructive shock or persistent hypotension defined as systolic blood pressure (BP) \<90 mmHg or an acute drop in systolic BP ≥40 mmHg for \>15 min, or requiring vasopressor or inotropic support to achieve a systolic BP ≥90 mmHg 3. Patients on ECMO 4. National Early Warning Score (NEWS) 2 ≥9 5. History, imaging or hemodynamic findings consistent with chronic thromboembolic pulmonary hypertension (CTEPH) or chronic thromboembolic disease (CTED) diagnosis 6. Imaging evidence or other evidence that suggests, in the opinion of the Investigator, that catheter-based intervention is not appropriate for the patient 7. Allergy, hypersensitivity, or heparin induced thrombocytopenia (HIT) 8. Contraindication or sensitivity to iodinated intravascular contrast that cannot be adequately premedicated 9. \<45 mL/min creatinine clearance 10. Severe active infection (e.g. sepsis) requiring treatment at time of enrollment 11. Active bleeding or disorders contraindicating anticoagulant therapy 12. Hemoglobin \<10 g/dL 13. Platelets \<100,000/μL 14. INR \>3 15. Cardiovascular or pulmonary surgery within last 7 days 16. Primary brain or metastatic brain cancer 17. Life expectancy \<90 days 18. Pregnancy 19. Intracardiac thrombus (right atrium, right ventricle clot in transit) or thrombus in the inferior vena cava identified on baseline imaging 20. Current participation in another investigational drug or device trial that may confound the results of this trial. Studies requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational studies. 21. Other medical, social, or psychological conditions that, in the opinion of the Investigator, precludes the patient from appropriate consent, could limit the patient's ability to participate in the trial, including compliance with follow-up requirements, or that could impact the scientific integrity of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in RV/LV Ratio | 48 hours post-randomization | Change in RV/LV ratio at 48 hours on original therapy as assessed by computed tomography pulmonary angiography (CTPA). Negative change values represent a reduction in the ratio of right ventricular to left ventricular diameter, consistent with improvement in right ventricular dilation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Outcome Assessment With the New York Heart Association Classification | Through 90 days post-randomization | Functional outcome as assessed by the New York Heart Association classification (NYHA) through 90 days. The New York Heart Association classification ranges from Class I (no limitations) -IV (severe limitation), with higher classifications being worse. |
| Functional Outcome Assessment With the Post Venous Thromboembolism Functional Status Scale | Through 90 days post-randomization | Functional outcome as assessed by the Post Venous Thromboembolism Functional Status (PVFS) scale through 90 days. The Post Venous Thromboembolism Functional Status scale ranges from 0-5, with higher scores being worse. |
| Functional Outcome Assessment With the Modified Medical Research Council Dyspnea Scale | Through 90 days post-randomization | Functional outcome as assessed by the modified Medical Research Council Dyspnea Scale (mMRC) through 90 days. The modified Medical Research Council Dyspnea Scale ranges from 0-4, with higher scores being worse. |
| Functional Outcome Assessment With the Borg Scale | Through 90 days post-randomization | Functional outcome as assessed by the Borg Scale through 90 days. The Borg Scale ranges from 0-10, with higher scores being worse. |
| Quality of Life Assessment With the Pulmonary Embolism Quality of Life Questionnaire | Through 90 days post-randomization | Quality of Life (QoL), as assessed by the Pulmonary Embolism Quality of Life Questionnaire (PEmb-QoL) through 90 days. The Pulmonary Embolism Quality of Life Questionnaire measures the percent of life affected by PE across 6 dimensions (including: Frequency of complaints, Limitations in activities of daily living (ADL), Work-related problems, Social limitations, Intensity of complaints, Emotional complaints), with higher scores being worse. |
| Quality of Life Assessment With the EQ-5D-5L Questionnaire | Through 90 days post-randomization | Quality of Life (QoL), as assessed by the EQ-5D-5L Questionnaire through 90 days. The EQ-5D-5L index is a preference-weighted measure of health status derived from five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Index values represent overall health status, with higher scores indicating better health status. The Visual Analogue Scale (VAS) scale is part of the questionnaire and ranges from 0-100, with higher scores being better. |
| All-cause Mortality | within 90 days post-randomization | All-cause mortality within 90 days |
| PE-related Mortality | within 90 days post-randomization | PE-related mortality within 90 days |
| Symptomatic PE Recurrence | within 90 days post-randomization | Symptomatic PE recurrence within 90 days |
| Functional Outcome Assessment With the 6-minute Walk Test | Through 90 days post-randomization | Functional outcome as assessed by the 6-minute walk test (6MWT) through 90 days. The 6-minute walk test measures distance walked in meters, with longer distances being better. |
| Major Adverse Events | within 7 days post-randomization | Major adverse events (MAEs) within 7 days: a composite of clinical deterioration requiring escalation of care, PE-related mortality, symptomatic recurrent PE, or major bleeding |
Countries
Canada, New Zealand, Poland, United States
Contacts
PRINCIPAL_INVESTIGATORRachel Rosovsky, MD
Massachusetts General Hospital
PRINCIPAL_INVESTIGATORRobert Lookstein, MD
MOUNT SINAI HOSPITAL
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 13.22 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 13 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not collected due to local privacy regulations | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 86 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 5 Participants |
| Race/Ethnicity, Customized White | 22 Participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 53 | 4 / 47 |
| other Total, other adverse events | 5 / 53 | 8 / 47 |
| serious Total, serious adverse events | 14 / 53 | 11 / 47 |
Outcome results
None listed