To determine whether CDT in high-risk PE relative to systemic thrombolysis is:- more effective and safer in terms of a reduction of the composite endpoint on all-cause mortality and adverse events defined as treatment failure, major bleeding and all…
ID
Source
Brief title
Condition
- Vascular therapeutic procedures
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the 30-day composite incidence of the binary endpoints
of
1) all-cause mortality
2) treatment failure
3) major bleeding
4) and all-cause stroke
Secondary outcome
The secondary endpoints are:
- Survival at day 7 and day 30
- Treatment failure at day 7 and day 30
- All-cause mortality at day 7, day 30 and day 90
- All-cause stroke at day 7 and day 30
- The composite incidence of the binary endpoints of all-cause mortality,
treatment failure, major bleeding and all-cause stroke at day 7
- Desirability of Outcome Ranking (DOOR) at day 722
- BARC3b and BARC3c bleeding, at day 7 and day 30
- ISTH major and non-major clinically relevant bleeding at day 7 and day 30
- Oxygen supplementation (LO2/min) at 48 hours
- Length of stay (days) at the ICU and in hospital at day 30
- Quality of life, functional status and symptom burden symptom burden at day 7
and after 3, 6, 9 and 12 months according to the ICHOM-VTE set
- Cost-effectiveness analysis after a time horizon of one year and budget
impact analysis
Background summary
Patients with high-risk pulmonary embolism (PE) require immediate reperfusion
therapy on top of anticoagulation. The standard reperfusion treatment in these
patients is full-dose systemic thrombolysis. This carries a significant risk of
major bleeding (10-25%) and intracranial haemorrhage (ICH, 3%).
Catheter-directed thrombectomy (CDT) is a promising alternative to systemic
thrombolysis with a more direct effect on reducing pulmonary artery clot burden
and very likely a better safety profile. Randomized trials evaluating the
safety and efficacy of CDT in high-risk patients are currently unavailable. We
hypothesize that in high-risk PE patients, CDT is superior to the current
standard of systemic thrombolysis in terms of mortality and adverse events,
i.e., is associated with a lower composite incidence of all-cause mortality,
treatment failure, major bleeding and all-cause stroke. We also hypothesize
that CDT will lead to a shorter length of stay (LOS) at the intensive care unit
(ICU) and in-hospital, faster recovery, and better long-term quality of life
(QoL).
Study objective
To determine whether CDT in high-risk PE relative to systemic thrombolysis is:
- more effective and safer in terms of a reduction of the composite endpoint on
all-cause mortality and adverse events defined as treatment failure, major
bleeding and all-cause stroke at day 30 (primary outcome)
- leads to a better Desirability of Outcome Ranking (DOOR) at day 7
- associated with a lower level of oxygen supplementation at 48 hours
- associated with shorter length of stay (LOS) at the intensive care unit (ICU)
and in the hospital
- associated with better functional recovery as well as better patient-reported
outcomes such as QoL at one year
- cost-effective after a time horizon of one year
Study design
TORPEDO-NL will be an investigator-initiated, academically sponsored,
multicentre, open-label, randomized controlled trial (RCT) designed to show
superiority of CDT (2 systems; technical variant) on top of regular
anticoagulation over systemic thrombolysis plus regular anticoagulation in
patients with high-risk PE in the Netherlands. A 2:1 (thrombectomy: systemic
thrombolysis) randomization will be applied. The randomization procedure will
be web-based, using randomly sized blocks consisting of 3,6 or 9 patients.
Randomization will occur after the verification that a thrombectomy procedure
can be started (randomization-to-needle time) within 60 minutes. Randomization
will be stratified by centre.
Intervention
The intervention consists of immediate thrombectomy (FlowTriever, Inari Medical
or Indigo, Penumbra Inc.) without systemic/locally administered thrombolysis.
Thrombectomy is performed via jugular or femoral venous access by an
interventional cardiologist, interventional radiologist or vascular surgeon
according to the instructions for use (IFU) for the particular device. The
catheter is advanced over a preplaced guidewire across the right heart into the
pulmonary arteries to the location of proximal thrombus. Procedural therapeutic
anticoagulation with heparin is administered. After removal of the dilator, the
thrombus is extracted by controlled volume aspiration through an aspiration
catheter using a syringe or dedicated aspiration system, with multiple
aspirations performed as needed. Procedural objectives will be clearly stated
prior to the intervention and patient*s clinical and hemodynamic status and
residual thrombus will guide the investigators to determine when to terminate
the procedure. Treatment success is defined as clear evidence of right
ventricular recompensation. The procedure must be discontinued in case of
treatment failure, i.e. lack of improvement or hemodynamic deterioration, and
major CDT complications such as cardiac arrest or severe haemoptysis.
Complications will be solved directly, with a procedure/treatment best suitable
according to the treating physician, to minimalize the risk of damage and
promote patient recovery.
Study burden and risks
Thrombectomy requires a procedure but may in part prevent the bleeding risks
associated with systemic thrombolysis. Further, patients will be followed for 1
year and asked to complete a set of patient reported outcome measures several
times. Benefit for patients involves a potentially lower mortality and
incidence of treatment failure and/or adverse events, lower short-term oxygen
requirement, a faster and better relief of functional limitations, a shorter
LOS, at the ICU and in-hospital, and better long-term outcomes of care.
Albinusdreef 2
Leiden 2300RC
NL
Albinusdreef 2
Leiden 2300RC
NL
Listed location countries
Age
Inclusion criteria
1. Adult patients with confirmed acute PE, i.e. contrast filling defect in a
lobar or more proximal pulmonary artery on computed tomography pulmonary
angiography (CTPA), and/or ob-structive shock with echocardiographic confirmed
dilatation of the right ventricle and a con-gested vena cava inferior, both
with/without echocardiographic signs of clot in transit or deep vein thrombosis
of the leg.
2. High risk for mortality, i.e.
a. post cardiac arrest (after temporary need for cardiopulmonary
resuscitation), OR
b. obstructive shock (systolic blood pressure <90 mmHg and signs of end-organ
hypoperfusion (e.g. elevated lactate levels >2 mmol/l) or the need for
vasopressors (adrenalin or noradrenalin) to maintain an adequate blood
pressure), OR
c. persistent hypotension (systolic blood pressure <90 mmHg or systolic blood
pres-sure drop >=40 mmHg for at least 15 minutes) not caused by new onset
arrhythmia, hypovolemia, or sepsis, OR
d. abnormal RV function on transthoracic echocardiography or CTPA AND elevated
cardiac troponin levels AND respiratory failure defined as hypoxemia (SaO2
<90%) refractory to O2 supplementation by nasal cannula or Venturi mask,
requiring full face mask O2 supplementation (100% FiO2), high-flow nasal O2, or
(non-)invasive mechanical ventilation.
3. CDT available and technically feasible so as to allow for a
randomization-to-needle time of 60 minutes or less.
Exclusion criteria
1. Adult patients with confirmed acute PE, i.e. contrast filling defect in a
lobar or more proximal pulmonary artery on computed tomography pulmonary
angiography (CTPA), and/or obstructive shock with echocardiographic confirmed
dilatation of the right ventricle and a congested vena cava inferior, both
with/without echocardiographic signs of clot in transit or deep vein thrombosis
of the leg.
2. High risk for mortality, i.e.
a. post cardiac arrest (after temporary need for cardiopulmonary
resuscitation), OR
b. obstructive shock (systolic blood pressure <90 mmHg and signs of end-organ
hypoperfusion (e.g. elevated lactate levels >2 mmol/l) or the need for
vasopressors (adrenalin or noradrenalin) to maintain an adequate blood
pressure), OR
c. persistent hypotension (systolic blood pressure <90 mmHg or systolic blood
pressure drop >=40 mmHg for at least 15 minutes) not caused by new onset
arrhythmia, hypovolemia, or sepsis, OR
d. abnormal RV function on transthoracic echocardiography or CTPA AND elevated
cardiac troponin levels AND respiratory failure defined as hypoxemia (SaO2
<90%) refractory to O2 supplementation by nasal cannula or Venturi mask,
requiring full face mask O2 supplementation (100% FiO2), high-flow nasal O2, or
(non-)invasive mechanical ventilation.
3. CDT available and technically feasible so as to allow for a
randomization-to-needle time of 60 minutes or less.
Exclusion criteria
1. *Catastrophic PE*, i.e. ongoing cardiac arrest and/or need for
extracorporeal cardiopulmonary resuscitation (ECPR) and/or immediate indication
for venoarterial extracorporeal membrane oxygenation (VA-ECMO) as judged by the
responsible physician(s)
2. Glascow Coma Scale <8 following resuscitation for cardiac arrest
3. Alternative diagnosis than acute PE contributing largely to the acute
hemodynamic and/or respiratory failure, e.g. sepsis, COPD GOLD 3 or 4, or known
heart failure with NYHA Functional Classification of 4, as judged by the
treating physician.
4. A known *do not admit to the ICU* or *do not resuscitate* directive
5. An absolute contraindication to systemic thrombolysis, i.e.
- History of hemorrhagic stroke
- Ischemic stroke in past 6 months
- Central nervous system neoplasm
- Major trauma, major surgery or major head injury in past 3 weeks (note: mild
external laceration of the head after, e.g. syncope, does not count as major
head injury, especially when a CT scan of the head shows no hematoma)
- Active bleeding, life-threatening or into a critically organ/area; OR known
severe bleeding diathesis with previous bleeding fulfilling these criteria
6. Reperfusion therapy (systemic thrombolysis, surgical thrombectomy or
CDT/other catheter directed therapy), or placement of a non-retrieved inferior
vena cava filter for acute pulmonary embolism in the past 3 months
7. Thrombus in transit through a patent foramen ovale.
8. Known chronic thromboembolic pulmonary hypertension (CTEPH), or strong
suspicion of CTEPH based on pre-existing clinical findings and combinations of
signs of PE chronicity on echocardiography and/or CTPA.
9. Known hypersensitivity to systemic thrombolysis, heparin, or to any of the
excipients
10. If, in the Investigator*s opinion, or after consultation with the local
PERT-team or EC-members, the patient is not appropriate for thrombectomy
11. Chronic use of full-dose oral or parenteral anticoagulation before
presentation.
12. Pregnancy
13. Current participation in another study that would interfere with
participation in this study
14. Previous enrolment in this study
15. Refusal of deferred consent by the next of kin or by the patient himself to
use the data. Deferred consent will not be asked to relatives of patients who
die in scene, but are included in the study.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
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In other registers
| Register | ID |
|---|---|
| CCMO | NL87503.058.24 |