To study the effects of left ventricular unloading by means of IABP or Impella as an adjunct to ECMO versus ECMO alone on ECMO weaning success, mortality, quality of life and cost-effectiveness, and intermediating physiological parameters.…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Successful ECMO weaning at 30 days, defined by; a) being alive, b) without
ECMO, IABP or Impella support, and c) not having received a heart
transplantation or left ventricular assist device (LVAD).
For the physiological substudy:
The difference in left ventricular end diastolic volume (as estimated by
transesophageal echocardiography) measured at the first time point (after
hemodynamic stabilization (defined by stable hemodynamic parameters such as
blood pressure and heart rate, and adequate ECMO flow) and within 24h after
ECMO initiation) in the cohort of patients supported by V-A ECMO with- versus
without- IABP at baseline (mechanical ventilation set at clinical PEEP).
Secondary outcome
1.. Treatment failure defined by: insertion of an IABP (only in the ECMO alone
arm), Impella (IABP unloading arm) or left atrial/ventricular vent
(in all arms).
2. 30 day, 90 day, and 1 year mortality,
3. ECMO support duration,
4. ICU- and hospital- admission duration,
5. The occurrence of major bleeding events (fatal, in a critical area
(intracranial, intraspinal, or intraocular), requiring intervention (coiling or
surgery)
and/or transfusion of >=3 packed cells) during or until 24 hours after
ECMO- or IABP-support, whichever comes last. (22)
6. Unplanned surgical or catheter based intervention of the leg(s) in which
ECMO and/or IABP was inserted during, or until 24 hours after ECMO- or
IABP-support, whichever comes last.
7. Time to lactate normalization (<2 mmol/L).
8. Time to first negative net fluid balance (counted per 24 hours).
9. The occurrence of continuous venovenous hemofiltration (dialysis) (CVVH(D))
initiation during ECMO support.
10. Course in PF ratio during ECMO support.
11. Duration of mechanical ventilation. Patients on mechanical ventilation via
tracheostomy need to be 24 hours free of mechanical ventilation.
12. Left ventricular ejection fraction 30 days after ECMO initiation.
13. Time course in vasoactive inotropic score (VIS) during ECMO support
14. Quality of life (QoL on basis of EQ5D questionnaires) after 1 year.
15. Total health care costs based on validated questionnaires (iMCQ and iPCQ)
at 6 months and 12 months follow up.
For the physiological substudy:
1. Heart rate
2. Pulmonary artery catheter: pulmonary capillary wedge pressure, cardiac
output, central venous pressure
3. Echocardiography: Left ventricular ejection fraction, TAPSE, VTI LVOT
4. Microcirculation measurements: Perfused vessel density (PVD [mm/mm2], Total
vessel density (TVD [mm/mm2],
5. Respiratory: FiO2, PEEP, Respiratory System Compliance (CRS) as the ratio
between Vt/Dp.
6. Laboratory: delta NT-pro BNP
Background summary
Extracorporeal membrane oxygenation (ECMO) can be of lifesaving effect in
patients with severe and refractory circulatory and/or respiratory failure.
Nevertheless, even today, 30-70 percent of patients cannot be weaned from ECMO
support and up to 50 percent of all patients die within one year. These high
weaning failure- and mortality- rates seem in part attributable to the
occurrence of major complications.
One of the inherent problems related to the application of venoarterial (VA)
ECMO in the context of a failing heart pertains to the occurrence of left
ventricular (LV) overload. Higher afterload can contribute to an increased
myocardial oxygen demand and higher LV end-diastolic pressure causing LV
dilatation, pulmonary oedema and thrombi in the heart and aortic root.
Eventually, this could lead to failure to wean from ECMO and an increased
mortality risk.
Several strategies could reduce or mitigate the effects of LV overload, so
called *unloading*. Unloading of the LV can be achieved by placing an
intra-aortic balloon pump (IABP) or an Impella in conjunction with VA ECMO.
Several observational studies have suggested that addition of an IABP or
Impella on top of ECMO may significantly reduce ECMO support duration and
improve survival, especially when used in a prophylactic fashion and as soon as
possible. Findings from these studies must however be interpreted with great
caution because of the effects of confounding by indication and selection bias.
Also, LV unloading through mechanical devices is associated with higher rates
of complications including bleeding, ischemia of the leg, haemolysis and
infection.
This randomized clinical trial will serve to randomize the existing variation
in treatment practice regarding the placement of an IABP or Impella as an
adjunct to VA ECMO, and thereby infer a conclusion on the best strategy.
Physiological effects of IABP in patients receiving V-A ECMO
In patients with refractory cardiac arrest and profound cardiogenic shock
undergoing V-A ECMO, a complex pathophysiological interaction is set between
the mechanically assisted heart and other organ systems, such as the
mechanically ventilated lungs and the circulatory system (macro- and
micro-circulation). This pathophysiological framework becomes even more complex
with the addition of an extra mechanical unloading device, such as the IABP.
The effects of IABP as adjunct to V-A ECMO on physiological variables have
never been studied in a randomized way. The framework of this platform and the
currently undergoing RCT enable us to add a physiological substudy to the this
trial that assesses the physiological impact of IABP in the context of V-A ECMO
on respiratory and hemodynamic.
Study objective
To study the effects of left ventricular unloading by means of IABP or Impella
as an adjunct to ECMO versus ECMO alone on ECMO weaning success, mortality,
quality of life and cost-effectiveness, and intermediating physiological
parameters.
Physiological substudy
To assess the effects of left ventricular unloading through IABP, in the
setting of VA ECMO support, on cardiovascular and respiratory physiology by
integrating a physiological substudy (by additionally recording physiological
parameters which are already collected in light of clinical routine).
Study design
An open-label, multicentre, response-adaptive, randomized clinical trial
studying the effects of left ventricular unloading by means of IABP or Impella
as an adjunct to ECMO versus ECMO alone on ECMO weaning success. This trial
will implement a contemporary Bayesian approach.
Physiological substudy:
A nested physiological observational substudy within the ongoing REMAP ECMO
RCT, using the trial arms where patients are randomized between receiving V-A
ECMO with or without IABP in two of the participating centres (Erasmus MC and
Haga hospital)
Intervention
The LV unloading trial domain will study the effects of ECMO + IABP vs ECMO +
Impella vs ECMO alone on weaning success and will encompass three arms:
1. *ECMO alone arm*: VA ECMO without mechanical unloading
2. *IABP unloading arm*: the combination of VA ECMO with an IABP.
3. * *Impella unloading arm*: the combination of VA ECMO with an Impella.
*During the trial, an *Impella unloading arm* will be added. Specifics of the
integration of this arm will be provided in an amendment during the study.
Study burden and risks
potential risks are considered moderate at maximum as a majority of patients
already receive an IABP or Impella in all centres. Patient burden is also
considered small for the same reason and the fact that no additional transports
are required. In addition, patients suffer from a severely reduced state of
consciousness due to the effects of sedation and severity of their illness.
Performing transesohageal echocardiography and a decremental PEEP trial are all
done in light of standard of V-A ECMO care. Patients will therefore not be
exposed to additional risks.
Sublingual measurements of the microcirculation are currently already applied
in the ICU setting but is not routinely used in all patients. These
measurements therefore represent the only extra measurements collected outside
of standard clinical practice. Sublingual measurements are non-invasive and
there are no risks associated with this monitoring device. Patients won*t
notice it because they suffer from a severely reduced state of consciousness,
due to deep sedation and the severity of their illness. There is no additional
burden related to microcirculation measurements.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
- Having received ECMO support for severe circulatory and/or respiratory
insufficiency.
- Age >= 18 years
- Cardiogenic shock
- Initiation of intra-aortic balloon pump (IABP) possible <= 8 hours after ECMO
initiation
Exclusion criteria
- Raised objection during the deferred consent procedure
- ECMO usage confined to the period during surgery or another intervention (the
ECMO was
removed at the end of the intervention).
- Isolated right ventricular failure (e.g. due to pulmonary embolism).
- Left ventricular assist device (LVAD), Impella or IABP in situ.
- Ventricular septal defect or papillary muscle rupture as the cause of shock.
- Thoracic or abdominal aortic dissection.
- Moderate or severe aortic regurgitation
- Mechanical prosthesis in mitral valve position
- Pregnancy
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 |
|---|---|
| ClinicalTrials.gov | NCT05913622 |
| CCMO | NL82979.078.23 |