Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03664557 |
| Other study ID # |
ReaReboa |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 26, 2018 |
| Est. completion date |
December 19, 2019 |
Study information
| Verified date |
November 2020 |
| Source |
University Hospital Inselspital, Berne |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Outcome after non-traumatic cardiac arrest remains poor despite many efforts in improving
immediate advanced life support (ALS) and post-arrest therapy. Preserving myocardial and
cerebral perfusion in the event of cardiac arrest by the means of effective cardio-pulmonary
resuscitation (CPR) is of utmost importance. During CPR, coronary perfusion pressure is a
significant predictor of increased rates of return of spontaneous circulation (ROSC) and
survival to hospital discharge, while cerebral perfusion pressure is crucial for good
neurologic outcome. The absence of ROSC despite prolonged high quality and efficient initial
basic life support (BLS) followed by traditional ALS ends finally in neuronal damage and
death. Occlusion of the aorta using a REBOA catheter in the management of noncompressible
abdominal or pelvic hemorrhage has shown improvements in hemodynamic profiles and has proved
to be feasible in both, clinical and preclinical settings for trauma patients in hemorrhagic
shock. Animal models of continuous balloon occlusion of the aorta in non-traumatic cardiac
arrest have shown meaningful increases in coronary artery blood flow, coronary artery
perfusion pressure and carotid blood flow, leading to improved rates of ROSC, 48h-survival
and neurological function. These promising data provide an opportunity to improve outcome
after cardiac arrest in humans too. Before testing such an approach in humans, the safe and
reliable placement procedure of the catheter-balloon in humans after cardiac arrest needs to
be established under ongoing CPR.
Description:
Background and Rationale Outcome after non-traumatic cardiac arrest remains poor despite many
efforts in improving immediate advanced life support (ALS) and post-arrest therapy.
Preserving myocardial and cerebral perfusion in the event of cardiac arrest by the means of
effective cardio-pulmonary resuscitation (CPR) is of utmost importance. During CPR, coronary
perfusion pressure is a significant predictor of increased rates of return of spontaneous
circulation (ROSC) and survival to hospital discharge, while cerebral perfusion pressure is
crucial for good neurologic outcome. The absence of ROSC despite prolonged high quality and
efficient initial basic life support (BLS) followed by traditional ALS ends finally in
neuronal damage and death. Occlusion of the aorta using a REBOA catheter in the management of
non-compressible abdominal or pelvic haemorrhage has shown improvements in hemodynamic
profiles and has proved to be feasible in a preclinical setting for trauma patients in
haemorrhagic shock. Animal models of continuous balloon occlusion of the aorta in
non-traumatic cardiac arrest have shown meaningful increases in coronary artery blood flow,
coronary artery perfusion pressure and carotid blood flow leading to improved rates of ROSC,
48h-survival and neurological function. These promising data provide an opportunity to
improve outcome after cardiac arrest in humans too. Before testing such an approach in
humans, the safe and reliable placement procedure of the catheter-balloon in humans after
cardiac arrest needs to be established under ongoing CPR.
Investigational Product (treatment, device) and Indication The ER-REBOA™ Catheter, Prytime
Medical, 229 North Main Street, Boerne, TX 78006, USA, has a CE Declaration of Conformity and
is intended, as defined in the instruction manual, for temporary occlusion of large vessels
and blood pressure monitoring. The ER-REBOA™ Catheter is specifically designed for use in the
emergency and critical care environment and was developed to support rapid and immediate
haemorrhage control in trauma patients but can also be used in patients with ruptured
aneurysms of the abdominal aorta. Importantly, the ER-REBOA™ Catheter is indicated to be
safely and effectively placed with or without the aid of medical imaging if none is
available. The device will be placed via femoral artery directly in the thoracic part of the
aorta, with the aid of a standard 7-F introducer sheath. For blood pressure monitoring
standard equipment (transducer and 0.9% saline flush unit) are required.
Puncture of the femoral artery to gain access to the arterial system is a standard procedure
in the emergency and critical care area, as well as in cardiology, interventional radiology,
angiology/vessel surgery and anaesthesiology. Puncture itself can be difficult or impossible,
even with the aid of ultrasonography, especially in an emergency. Nevertheless, even
prehospital puncture of the femoral artery during cardiac arrest in order to obtain
hemodynamic monitoring and guide CPR has shown feasible. Handling the balloon catheter
requires a short introduction and some mannequin training before first use.
Preclinical Evidence Several studies have examined the effect of continuous balloon occlusion
of the aorta during non-traumatic cardiac arrest in animal models. Occlusion of the aorta
with and without selective aortic arch perfusion was shown to increases coronary artery blood
flow and perfusion pressure as well as carotid perfusion pressure and blood flow, thus
leading to improved rates of ROSC, 24h- and 48hsurvival and neurological function in animals.
To the investigators' knowledge, no conflicting data failing to show the described effects
has been published, leading to the suggestion that further research should concentrate on the
question whether these promising findings apply for humans, too.
Clinical Evidence to Date Recent advances in technology have led to the endovascular approach
to the aorta being no longer exclusively the domain of cardiology, angiology and vascular
surgery, but emergency and critical care physicians and surgeons using the technique in the
emergency and critical care setting as well as in a prehospital setting to control major
pelvic and abdominal hemorrhage in trauma victims. Therefore, regarding the use of the
ER-REBOA catheter, available literature reports mainly trauma victims, where endovascular
occlusion of the aorta was used to control exsanguinating hemorrhage but was also shown to
lead to meaningful increases of mean arterial blood pressure immediately following occlusion
of the aorta. A recent study examining the outcome of trauma victims with severe hemorrhage
also included patients in traumatic cardiac arrest and showed a neurological intact survival
rate of 10%, whereas survival of cardiac arrest due to massive hemorrhage treated with
emergency department thoracotomy with aortic cross-clamp is known to be dismal. Similarly,
patients with non-traumatic hemorrhage mainly from intraabdominal aneurysmal rupture received
REBOA until definitive hemorrhage control, with 7 of 11 patients being in cardiac arrest at
the time of insertion and a high survival rate of 57%. Regarding cardiac arrest not
associated with hemorrhage and/or trauma, for humans only case reports exist, describing
neurological intact survival in one case of refractory cardiac arrest with PEA/Asystole
during coronary angiography, where after 20 minutes of futile ALS an intra-aortal balloon
pump (IABP) was inserted, with detection of ROSC 30seconds after occlusion of the descending
aorta. Importantly, the estimated benefit of increased mean arterial pressure and coronary
perfusion pressure even with intermittent occlusion of the aorta has led to the
recommendation to use the IABP (after switching to a pressure-triggered mode) in patients
with cardiac arrest after heart surgery and IABP in place.
Medical Device: Rationale for the intended purpose in study (pre-market MD) The ER-REBOA™
Catheter was chosen because it is (to the investigators' knowledge) the only REBOA catheter
which can be inserted without a guide wire, and the placement does not necessarily need
radiologic guidance.
Risks / Benefits As only patients will be included who have failed to respond to recommended
standard resuscitation therapy (refractory cardiac arrest under BLS/ALS) and not qualifying
for e-CPR, these patients can only gain the benefit of improved survival to hospital
discharge and neurological good outcome, given the extremely poor chance of neurologic intact
survival otherwise. This outweighs the risks associated with arterial puncture (damage to the
vessel/ tissue, pseudoaneurysma, fistula, surgical repair after successful resuscitation) and
the theoretical risk of limb paralysis after prolonged (> 2 hours) ischemia.
Survival of cardiac arrest with an unwanted unfavorable neurologic state is an inherent risk
of resuscitation per se. Use of a REABOA device might possibly shift patients from the
out-come groups "death" towards "vegetative state" or "home-bound and dependent on others".
The investigators cannot estimate this specific "risk of survival", which, depending on
personal beliefs, are not necessarily seen as bad outcome at all.
As described above, the ER-REBOA™ Catheter is intended for temporal occlusion of large
vessels and specifically designed for the use in an emergency or intensive care setting, as
it is planned in this study. Possible problems with malpositioning and injury to the access
site, rarely requiring surgical repair, have been addressed. The extreme complication - the
case of exsanguinating hemorrhage due to the puncture - is judged acceptable by the study
group compared to the potential benefit of surviving otherwise refractory cardiac arrest
during standard ALS.
Justification of choice of study population To evaluate the feasibility of the REBOA catheter
placement during resuscitative efforts due to cardiac arrest, the investigators cannot
perform the study in already deceased persons since the investigators need the hemodynamic
measurements during CPR as a success parameter that measurable blood pressure can be
generated in the aorta due to the occlusion. Since cardiac arrest and CPR cannot be performed
in healthy subjects or in patients during routine cardiac surgery or coronary angiography,
the investigators can only perform the study in patients suffering from actual cardiac
arrest. Patients in cardiac arrest are per definition clinically dead (no circulation - no
breathing) and in the most extreme life threatening emergency. Therefore patients in CA
cannot consent beforehand. Standard CPR is a highly focused team-orientated and standardized
event to save the life of the patient, and given the nature of cardiac arrest, an extremely
time-sensitive emergency. It will therefore be no time to contact family members or next of
kin to get consent for a study, and timely involvement of an independent physician in the
study consent procedure beforehand will not be achievable in each case (despite the intend to
do so). If the patient survives, a daily assessment of the patient's capacity to give
informed consent will be done until the patient is discharged from the ICU, as in any case of
significant clinical change. When the patient is judged capable of giving consent, a post hoc
informed consent process will be performed as soon as possible. If the patient is permanently
lacking capacity to consent and if no written statement of wishes formulated in a state of
capacity is available, a proxy consent will be obtained from a person authorized to represent
the patient as soon as possible, bearing in mind the emotional stress the proxy experienced
after the event of sudden cardiac death and resuscitation and providing an appropriate time
frame.
