Phase 4
N=131
Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Pulmonary Embolism
Pulmonary Embolism and Thrombosis
Bottom Line
View on ClinicalTrials.gov: NCT02396758 ↗Enrolled (actual)
131
Serious AEs
32.6%
Results posted
Mar 2021
Primary outcome: Primary: Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio to 48 ± 6 Hours After the Start of the APT Procedure — 1.53; 1.47; 1.52; 1.51 ratio
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Ekosonic® Endovascular Device ultrasonic infusion catheter (Device); Recombinant tissue plasminogen activator (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Boston Scientific Corporation
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in the Right Ventricle (RV) Diameter-to-Left Ventricle (LV) Diameter Ratio to 48 ± 6 Hours After the Start of the APT Procedure |
1.53; 1.47; 1.52; 1.51; -0.43; -0.37 | — |
| PRIMARY Number of Participants With Major Bleeding Within 72 Hours After Initiating the APT Procedure |
0; 2; 1; 2 | — |
| SECONDARY Percentage of Participants With Treatment Success of an APT Procedure |
73.9; 68.0; 69.2; 61.6 | — |
| SECONDARY Change From Baseline in RV/LV at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph. |
1.19; 1.20; 1.13; 1.20; -0.23; -0.29 | — |
| SECONDARY Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph |
16.32; 17.20; 16.39; 18.02; 0.27; 0.79 | — |
| SECONDARY Change From Baseline in Estimated Right Ventricular Systolic Pressure (RVSP) at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph |
31.59; 36.64; 35.57; 25.75; -2.18; -10.87 | — |
| SECONDARY Percentage of Participants With Collapse of the Inferior Vena Cava (IVC) With Respiration at Days 0, 2, 30, 90, and 365, as Assessed by Echocardiograph |
96.55; 100.00; 96.00; 81.25; 89.66; 96.00 | — |
| SECONDARY Change From Baseline in Thrombus Burden by Miller Score as Assessed by Pulmonary Arteriogram (PAgram) at Day 0 |
23.71; 23.29; 24.21; 22.93; -1.00; -2.29 | — |
| SECONDARY Change From Baseline in Thrombus Burden by Modified Miller Score as Assessed by CTA Scan at 48 ± 6 Hours After the Start of the APT Procedure |
20.72; 20.00; 20.92; 20.44; -1.24; -2.20 | — |
| SECONDARY Change in 6 Minute Walk (6MW) Distance From Day 30 to Day 90 and 365 |
355.4; 366.90; 362.3; 327.3; 23.8; 70.6 | — |
| SECONDARY Change in Borg Scale Score Before and After 6MW Distance Test at Days 30, 90, and 365 |
0.75; 0; 0.5; 0; 0.25; 0 | — |
| SECONDARY Number of Participants Who Received Oxygen Therapy |
29; 30; 34; 10; 28; 30 | — |
| SECONDARY Change in Participant Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) 6b Score From Day 30 to Day 365 |
42.00; 43.86; 44.53; 41.40; 3.61; 4.91 | — |
| SECONDARY Change in Pulmonary Embolism Quality of Life (PEmb-QOL) Score From Day 30 to Day 365 |
38.30; 27.85; 24.25; 25.63; -16.79; -8.86 | — |
| SECONDARY Number of Participants Who Encountered Technical Procedural Complications |
0; 0; 1; 0 | — |
| SECONDARY Number of Participants With Symptomatic Recurrent Pulmonary Embolism (Per Adjudication) |
0; 1; 1; 0 | — |
| SECONDARY Number of Participants Who Die Due to Any Cause |
1; 1; 0; 1 | — |
| SECONDARY For Participants of UK Sites: Freedom From Major Harm Occurring Between Enrolment and 30 Days |
10; 9; 9; 0 | — |
| SECONDARY For Participants of UK Sites:Change in EuroQual - 5 Dimensions - 5 Levels (EQ-5D-5L) Score From Day 30 to Day 365 |
0.732; 0.819; 0.934; 66.7; 77.8; 82.5 | — |
| SECONDARY For Participants of UK Sites: Time From Hospital Admission to Diagnosis of PE |
10.77; 9.30; 7.29 | — |
| SECONDARY For Participants of UK Sites: Time From Diagnostic Computed Tomography (CT) Scan to Initiation of Treatment for PE |
25.33; 24.53; 30.08 | — |
| SECONDARY For Participants of UK Sites: Time in Each Level of Care (Level 0 and 1; Level 2; and/or Level 3) Through Discharge |
74.64; 57.04; 64.39; 86.77; 62.34; 94.56 | — |
| SECONDARY Healthcare Resource Utilization: Team Managing the Participant During Hospitalization - Number of Healthcare Professional (HCP) Specialties Involved. (UK Participants Only) |
3.9; 4.2; 4.0 | — |
| SECONDARY Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12month Follow-up. (UK Participants Only) |
1.5; 1.3; 1.0 | — |
| SECONDARY Healthcare Resource Utilization: Number of Healthcare Professionals (HCP) Visits for Venous Thromboembolism (VTE) After Hospitalization and During 12 Month Follow-up. (UK Participants Only) |
1.5; 1.3; 1.0 | — |
| SECONDARY Healthcare Resource Utilization: Number of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only) |
0; 0; 1; 0 | — |
| SECONDARY Healthcare Resource Utilization: Duration of Hospital Re-Admissions After Hospitalization and During 12 Month Follow-up. (UK Participants Only) |
2 | — |
Summary
The objective is to determine the optimum dose of thrombolytic and duration of the ultrasound procedure (together defined as the APT Procedure) as a treatment for acute submassive pulmonary embolism (PE). Symptomatic submassive PE are participants with acute (less than or equal to [≤]14 days) PE with normal systemic arterial blood pressure (greater than [>] 90 mmHg) and evidence of RV dysfunction (right ventricular to left ventricular diameter ratio, that is; RV/LV ratio greater than or equal to [≥] 0.9). Participants with submassive PE will be randomized to one of four APT treatment groups: ultrasound of 2 and 6 hours (hrs) with r-tPA 2 milligrams (mg)/hr/catheter and ultrasound 4 and 6 hours with r-tPA, 1 mg/hr/catheter. On 08 June 2016, randomization into treatment group 4 (APT/6 hours-r-tPA/2 mg/hr/catheter) was closed following a reported intracranial hemorrhage (ICH) and death in a study participant in this arm.
Eligibility Criteria
Inclusion Criteria
- Male or female greater than or equal to (≥) 18 years of age and less than or equal to (≤) 75 years of age.
- CTA evidence of proximal PE (filling defect in at least one main or lobar pulmonary artery).
- PE symptom duration ≤14 days.
- Submassive PE: RV/LV diameter ≥ 0.9 from CTA and hemodynamically stable. For Participants in UK Sites: Submassive PE: RV/LV diameter ≥ 0.9 from CTA, hemodynamically stable and an elevated biomarker.
- Must be treated within 48 hours of diagnosis of PE by CTA.
- Signed Informed consent obtained from subject or Legally Authorized Representative.
Exclusion Criteria
- Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year.
- Recent (within one month) or active bleeding from a major organ.
- Major surgery within seven days of screening for study enrollment.
- Clinician deems the subject high-risk for catastrophic bleeding.
- History of heparin-induced thrombocytopenia (HIT).
- Catheter-based pharmacomechanical treatment for PE within 3 days of study enrollment.
- Systolic blood pressure (SBP) less than 90 mm Hg and/or use of vasopressors.
- Cardiac arrest (including pulseless electrical activity and asystole) requiring active cardiopulmonary resuscitation (CPR).
- Evidence of irreversible neurological compromise.
- Life expectancy 3.
- Creatinine outside the normal range for the treating institution.
- Participant is pregnant (positive pregnancy test; women of childbearing capacity must be tested) or breast feeding.
- Active cancer (metastatic, progressive, or treated within the last 6 months). Exception: participants with non-melanoma primary skin cancers are eligible to participate in the study.
- Known allergy, hypersensitivity, or thrombocytopenia from heparin, r-tPA, or iodinated contrast except for mild-moderate contrast allergies for which steroid pre-medication can be used.
- History of any hematologic disease potentially involving abnormal platelet number or function.
Data sourced from ClinicalTrials.gov (NCT02396758). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.