The primary study objective is to compare the clinical outcomes of patients treated with the FlowTriever System versus Catheter-Directed Thrombolysis (CDT) for use in the treatment of acute intermediate-high-risk pulmonary embolism (PE).
ID
Source
Brief title
Condition
- Vascular therapeutic procedures
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is a composite clinical endpoint constructed as a win
ratio, a hierarchy of the following, assessed at hospital discharge or at 7
days after the index procedure, whichever is sooner:
1. All-cause mortality, or
2. Intracranial hemorrhage (ICH), or
3. Major bleeding per ISTH definition4, 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.
Secondary outcome
The secondary endpoints of the study will assess safety, effectiveness, and
utility measures, as follows:
* Composite clinical endpoint constructed as a win ratio hierarchy of the
following four components, assessed at hospital discharge or at 7 days after
the index procedure, whichever is sooner:
o All-cause mortality, or
o Intracranial hemorrhage (ICH), or
o Major bleeding per ISTH definition4, or
o Clinical deterioration defined by hemodynamic or respiratory worsening,
and/or escalation to a bailout therapy
* Individual components of the win ratio composite endpoint, assessed at
hospital discharge or at 7 days after the index procedure, whichever is sooner:
o All-cause mortality
o Intracranial hemorrhage (ICH)
o Major bleeding per ISTH4 definition
o Clinical deterioration defined by hemodynamic or respiratory worsening,
and/or escalation to a bailout therapy
o ICU admission and ICU length of stay during the index hospitalization and
following the index procedure
* All-cause mortality within 30 days from index procedure
* PE-related and all-cause readmission within 30 days from index procedure
* Device and drug-related serious adverse events through the 30 day visit
* Clinically Relevant Non-Major (CRNM) and Minor bleeding events through
hospital discharge or at 7 days after the index procedure, whichever is sooner
* Change in right-ventricular/left-ventricular (RV/LV) ratio from baseline to
24 hour visit, as measured by echocardiography or CT
* mMRC Dyspnea score at 24 hour visit and 30 day visit
* Length of total hospital stay and post-index-procedure hospital stay (to a
maximum of 30 days)
* Disease-specific and general health-related quality of life at the 30 day
visit (PEmb-QoL and EQ-5D-5L)
Background summary
Pulmonary embolism (PE) is a debilitating and potentially lethal disease,
leading to an estimated 300,000 hospitalizations per year in the US, and over
400,000 PE events in Europe in 2004 with 10-30% mortality. PE and deep vein
thrombosis (DVT) are the 2 main clinical consequences of venous thromboembolism
(VTE), which together lead to over 500,000 annual hospitalizations in the US,
and a similar number in Europe. While a reduction in mortality was seen over
that time period, mortality in 2012 still ranged from 1.6% to 39.1%, depending
on the severity of the disease. While small PEs may remain asymptomatic and go
unnoticed, larger emboli can result in significant pulmonary artery
obstruction, leading to right heart decompensation and mortality. The goal of a
successful interventional procedure is to restore RV outflow through the
pulmonary artery, thereby disrupting the potentially lethal cascade towards
hemodynamic collapse. However, there remains a strong clinical need to develop
a reliable, rapid, percutaneous method of thrombus removal for the treatment of
clinically significant acute PE. The need is especially strong for a mechanical
method that does not rely on the use of thrombolytics, as physicians are
reluctant to administer thrombolytics given the high bleeding risk and because
many patients cannot tolerate lytics. The FlowTriever System was developed to
meet this need to rapidly restore blood flow through the pulmonary vasculature
in patients experiencing acute submassive or massive pulmonary embolism.
However, clinical data from prospective, randomized control trials are still
lacking for FlowTriever and other advanced therapies.
Study objective
The primary study objective is to compare the clinical outcomes of patients
treated with the FlowTriever System versus Catheter-Directed Thrombolysis (CDT)
for use in the treatment of acute intermediate-high-risk pulmonary embolism
(PE).
Study design
This study is a prospective, multicenter, randomized controlled trial of the
FlowTriever System compared to CDT for acute intermediate-high-risk PE, and
includes a non-randomized cohort for subjects with an absolute contraindication
to thrombolytics. The study will collect data on demographics, comorbidities,
details from the PE diagnosis and treatment, and clinical outcomes through
30-day follow up.
Randomized Controlled Trial Cohort (RCT Cohort):
This study is a prospective, multicenter, randomized controlled trial of the
FlowTriever System compared to Catheter-Directed Thrombolysis (CDT) for
treatment of acute intermediate-high-risk PE.
Non-Randomized Absolute Contraindication to Thrombolytics Cohort
(Contraindication Cohort):
Subjects who meet study eligibility criteria and who have an absolute
contraindication to thrombolytics, whose initial planned primary treatment
strategy includes FlowTriever, will be evaluated as part of the
Contraindication Cohort. The same RCT Cohort clinical assessments and follow up
schedule will be administered in this Contraindication Cohort.
Intervention
N/A
Study burden and risks
There is an optional invasive additional measurement for Catheter-directed
thrombolysis patients. Once the procedure is finished the catheters are
typically removed right away. Optionally and if really required, the post PA
pressure measurements can be collected but reopening of the access area would
be required (6 hours post procedure).
St. Jakobs-Strasse 7
Basel 4052
CH
St. Jakobs-Strasse 7
Basel 4052
CH
Listed location countries
Age
Inclusion criteria
Subjects must meet each of the following criteria to be included in the study:
1. Age * 18 years
2. Echo, computed tomographic pulmonary angiography (CTPA), or pulmonary
angiographic evidence of any proximal filling defect in at least one main or
lobar pulmonary artery
3. Classification of intermediate-high-risk PE by ESC Guidelines 20191,
including ALL of the following:
a. Clinical signs and symptoms consistent with acute PE, or PESI class III-V,
or sPESI *1
AND
b. Hemodynamically stable
AND
c. RV dysfunction on echocardiography or CT
AND
d. Elevated cardiac troponin levels
4. Intervention planned to begin within 72 hours of the later of either
a. Confirmed PE diagnosis
OR
b. If transferring from another hospital, arrival at the treating hospital
5. Symptom onset within 14 days of confirmed PE diagnosis
Exclusion criteria
Subjects will be excluded from the study for any of the following criteria:
1. Unable to anticoagulate with heparin, enoxaparin or other parenteral
antithrombin
2. Index presentation with hemodynamic instability that are part of the high-
risk PE definition in the ESC Guidelines 20191, including ANY of the following:
a. Cardiac arrest OR
b. Systolic BP < 90 mmHg or vasopressors required to achieve a BP *90 mmHg
despite adequate filling status, AND end-organ hypoperfusion
OR
c. 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
3. Known sensitivity to radiographic contrast agents that, in the
Investigator*s opinion, cannot be adequately pre-treated
4. 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)
5. Patient has right heart clot in transit identified at baseline screening
6. Life expectancy < 30 days (e.g stage 4 cancer or severe COVID-19 infection),
as determined by the Investigator
7. Current participation in another drug or device study that, in the
Investigator*s opinion, would interfere with participation in this study
8. Current or history of chronic thromboembolic pulmonary hypertension (CTEPH)
or chronic thromboembolic disease (CTED) diagnosis, per ESC 2019 guidelines1
9. Invasive systolic PA pressure *70 mmHg prior to study device entering the
body
10. Administration of bolus or drip/infusion thrombolytic therapy or mechanical
thrombectomy for the index PE event within 48 hours prior to enrollment
11. Ventriculararrhythmiasrefractorytotreatmentatthetimeofenrollment
12. Knowntohaveheparin-inducedthrombocytopenia(HIT)
13. 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)
14. Subject has previously completed or withdrawn from this study
15. Patient unwilling or unable to conduct the follow up visits per protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL81035.078.22 |