Primary objectives: 1. Safety 2. Practical feasibility Secondary objectives: 1. angiographic patency rate before PCI 2. Cumulative ST-segment resolution. 3. myocardial infarct characteristics 4. Myocardial perfusion on contrast echocardiography 5.…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Safety, assessed by the occurrence of ventricular arrhythmias defined as
sustained ventricular tachycardia and/or ventricular fibrillation and the
occurrence of shock defined as a systolic blood pressure (SBP) <100mmHg in
combination with tachycardia (HR > 100/min), after initiation of
sonothrombolysis and before percutaneous coronary intervention.
- Technical feasibility will be assessed by extent of sonothrombolysis
completion during ambulance transfer and quality of the images.
Sonothrombolysis completion will be measured by counting the number of applied
high MI impulses and quality of the images will be assessed by counting the
amount of visible segments during sonothrombolysis.
Secondary outcome
- Cumulative ST-elevation resolution
- Angiographic patency rate on coronary angiography
- Myocardial infarct size by delayed enhancement imaging, as well as the
salvageability index, defined as the difference between extent of delayed
enhancement by Gd MRI and the T2 weighted double or triple inversion spin echo
assessment of risk area, divided by the area at risk. Presence and extent of
myocardial injury. Scar size, LVEF and other quantitative assessments as
function of LV mass/volume.
- Frequency of left ventricular remodeling
- Myocardial perfusion on follow up contrast enhanced echocardiography
- Maximum CPK and troponin
- Occurrence of adverse events (AEs), serious adverse events (SAEs), suspected
unexpected serious adverse reactions (SUSARs) and six month event free
survival. AE is defined as any untoward medical occurrence in the patient
during the intervention period (one hour after sonothrombolysis initiation),
whether or not considered causally related to the intervention. SAE is defined
as any untoward medical occurrence that at any dose results in a
life-threatening situation or death, or requires (prolongation of)
hospitalization or results in a persistent or significant disability during 6
month follow up. SUSARs are defined as the occurrence of hypotension,
ventricular rhythm disorders, cardiac arrest and/or anaphylaxis within one hour
after sonothrombolysis initiation. Six-month event free survival is calculated
from treatment initiation to six months afterwards, where events include death,
congestive heart failure, life threatening arrhythmias, recurrence of ACS and
need for prophylactic defibrillator.
Background summary
The optimal treatment strategy in patients with acute ST-elevated myocardial
infarction (STEMI) is immediate restoration of epicardial coronary blood flow.
Thrombolytic therapy is the most widely used therapy, however, important
limitations are a relatively low recanalization rate, and hemorrhagic
complications. Currently, primary percutaneous coronary intervention (PCI) is
the treatment of choice in STEMI patients, however, its widespread use is
hampered by limited availability of specialized facilities and trained staff.
Also, peripheral microvascular obstruction often occurs, as part of the
microvascular injury pathway. Additional drugs can be administered in this
case, but detection of this obstruction is difficult, even with intracoronary
measurements using specialized wires. A method by which this microvascular
obstruction might be visualized is with ultrasound echocardiography and
ultrasound contrast agents (UCAs). Besides the added diagnostic value of
ultrasound contrast agents, the application of ultrasound and UCAs with and
without thrombolytic agents have been investigated and were found to enhance
thrombus dissolution in vitro and in vivo (sonothrombolysis). Pilot studies
also demonstrated that ultrasound and microbubbles might have a beneficial
effect on the microcirculation in humans. We consider the duration of patient
stay in the ambulance as a window of opportunity for the prePCI treatment.
Therefore the aim of this pilot study is to examine the safety, feasibility and
efficacy of pre-hospital (ambulance) sonothrombolysis for STEMI patients.
Study objective
Primary objectives: 1. Safety 2. Practical feasibility
Secondary objectives: 1. angiographic patency rate before PCI 2. Cumulative
ST-segment resolution. 3. myocardial infarct characteristics 4. Myocardial
perfusion on contrast echocardiography 5. left ventricular remodeling 6.
maximum CPK/troponin levels
Study design
The MRUSMI Ambulance Trial will be a single center safety and feasibility pilot
study, comparing prehospital sonothrombolysis and post-PCI sonothrombolysis
versus standard care in STEMI patients. There will be no control group in this
study. Instead we will use the patients randomized to the control group from
the MRUSMI post-PCI study, to set our results in perspective. The study will be
carried out in one of the ambulances of the ambulance station in Zaandam and in
the Amsterdam UMC - Location VUmc. A mobile echocardiography device will be
installed in the ambulance and vials of ultrasound contrast agents (Luminity ®)
and the vial activator (shaker) will be present in the ambulance. Education of
all emergency and ambulance staff in the ambulance post in Zaandam will be
required prior to study initiation, to ensure all eligible subjects are allowed
to participate and no delays in conventional therapy administration occur as a
consequence of participation. Ambulance staff will be trained to perform
parasternal short axis contrast ultrasound echocardiography and a physician
researcher will accompany ambulance personnel while including the first few
patients. Patients with STEMI who meet the inclusion criteria will be asked by
the physician researcher (and later on the ambulance personnel) to participate
in the MRUSMI ambulance study. This will only be asked if confirmation of STEMI
has taken place via Lifenet (system in which the ambulance ECG is faxed to the
hospital and interpreted by a physician, the physician confirms the STEMI ECG
and allows for the ambulance to bring the patient to the catheterization
laboratory). Obtaining informed consent in this way will ensure the subject is
receiving adequate information about the research protocol and yet treatment in
a timely fashion.
The patient will be informed about the study orally, as in the MRUSMI post PCI
trial:
*Beste mevrouw/ meneer,
Wij doen onderzoek naar een extra behandeling met echogeluid en microbellen bij
patiënten met een hartinfarct. Wij willen onderzoeken of deze behandeling een
beschermend effect heeft op de kleine vaten van het hart. De behandeling
bestaat uit het toedienen van microbelletjes via het infuus en het gelijktijdig
maken van een echo van het hart. Deze behandeling vindt nu plaats en duurt
ongeveer tot aankomst in het ziekenhuis. Het onderzoek geen significante
risico*s.
Na de behandeling krijgt u van ons een brief met nadere informatie en kunt u
deze rustig doornemen en vragen stellen indien nodig.
Zou u willen meedoen met het onderzoek?*
If oral informed consent is given, the intervention will be given approximately
30 minutes or until arrival at the hospital.The system utilized in the
ambulance will be the CX 50 Portable ultrasound system (Philips Healthcare)
operating at 1.8 MHz using the low MI mode with intermittent high MI impulses.
Upon arrival in the hospital standard care procedures will be performed (CAG +
PCI). After PCI, patients will be informed about the study and will be given
opportunity to ask about the protocol and to give written informed consent.
There will be no active randomization, instead patient outcomes will be
compared with the outcomes of the control group of the MRUSMI trial. Note that
all patients receive sonothrombolysis in the ambulance. The follow up
examinations are contrast enhanced echocardiography at 3-4 months, CMR at week
1 and after 6-8 weeks.
Intervention
Sonothrombolysis: contrast enhanced echocardiography with intermittent high MI
impulses (see above)
Study burden and risks
Use of ultrasound contrast agent with very small risk of allergic reaction and
reperfusion rhytm disturbances. The study will be performed in a safe
environment in the ambulance and on the coronary care unit. Instable patients
(cardiogenic shock etc.) will be excluded
An extra MRI will be made and an extra contrast echocardiography.
de Boelelaan 1117
Amsterdam 1081HV
NL
de Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
Patients presenting with STEMI with:, - >= 2mm ST-segment elevation in 2
anterior or lateral leads; or
- >= 1 mm ST-segment elevation in 2 inferior leads
- >= 1mm ST-segment elevation in lateral leads (I, aVL, V5, V6)
AND
- Within 12 hours of symptom onset
- Age >= 30 years
- Adequate apical and/or parasternal images by echocardiography
Exclusion criteria
- Previous coronary bypass surgery
- Cardiogenic shock
- Known or suspected hypersensitivity to ultrasound contrast agent used for the
study
- Known bleeding diathesis or contraindication to glycoprotein IIB/IIIA
inhibitors, anticoagulants or aspirin
- Known large right to left intracardiac shunts
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 |
|---|---|
| EudraCT | EUCTR2019-001883-31-NL |
| CCMO | NL69980.029.19 |