RecruitingACTRN12620000807954

The role of high power ultrasound in restoring blood flow for patients presenting with a major heart attack.

REstoring microvascular circulation with Diagnostic Ultrasound and Contrast agEnt (REDUCE): A multicentred, randomised, double blinded, controlled trial in patients presenting with ST elevation myocardial infarction.


Sponsor

University of Sydney

Enrollment

150 participants

Start Date

Aug 31, 2020

Study Type

Interventional

Conditions

Summary

Heart attack is the leading cause of morbidity and mortality globally, claiming 8,623 Australian lives in 2014 (i.e. 24 deaths/day). The heart attack is caused by the blockage of the blood flow in the heart, requiring emergent life-saving treatment to restore the blood flow using a balloon or a stent. For the last 30 years, however, death rates for the heart attack have not improved. One of the key reasons for this is the blockage of smaller micro-vessels of the heart. This micro-vessel abnormality occurs in up to 60% of patients with heart attacks and is independently associated with worse outcomes. Nevertheless, currently no established therapeutic options exist. Therefore, we will perform a prospective randomised controlled trial (RCT) to treat the micro-vessel blockages with a novel method using ultrasound with contrast agent (i.e. sonothrombolysis). Many animal studies have demonstrated that sonothrombolysis can break up blood clots of both large and small vessels, and improve the blood flow. A recent, single-centre human RCT led by Prof Porter in USA confirmed that sonothrombolysis opens the micro-vessel blockages after heart attack and improves the heart function. Next logical step is to evaluate this method in multicentre setting with a larger scale. After close communications with Prof Porter, we established our protocol for a prospective multicentre RCT with sham procedure to test our hypothesis that additional sonothrombolysis to standard treatment for heart attack would reduce heart muscle damage and improve heart function in short term and improve patient survival long term. We will run this trial across three Australian hospitals. We will be studying their outcomes during their hospital stay and following their progress with cardiac imaging over 6 months. The findings from this trial have the potential to significantly improve the overall prognosis for patients having a life-threatening heart attack and to change our standard of care and clinical guidelines.


Eligibility

Sex: Both males and femalesMin Age: 30 YearssMax Age: 80 Yearss

Plain Language Summary

Simplified for easier understanding

When a heart attack occurs, it happens because a blood clot blocks one of the arteries supplying the heart. Emergency treatment (like a stent or balloon procedure) can open that large blockage, but tiny micro-vessels deeper in the heart muscle often remain blocked — affecting up to 60% of heart attack patients — and there is currently no established treatment for this. This micro-vessel damage is linked to worse long-term outcomes. This trial is testing a technique called "sonothrombolysis" — using ultrasound combined with a contrast agent (tiny micro-bubbles) — to try to break up these micro-vessel clots. The ultrasound is delivered through a handheld probe on the chest alongside standard emergency treatment. Participants are randomly assigned to either receive the real sonothrombolysis or a sham (inactive) procedure, and their heart function is monitored through imaging over six months. You may be eligible if you are aged 30 to 80, are presenting to hospital with a heart attack (STEMI or posterior STEMI), and are eligible for emergency stenting or clot-dissolving treatment. People who have had a previous heart attack, are in cardiogenic shock, or have a known heart muscle disease would not be eligible. This study is being run across three Australian hospitals.

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Interventions

The intervention is the focused application of high mechanical index ultrasound to the heart while the patient is receiving an intravenous infusion of a microbubble contrast known as "Definity®". “

The intervention is the focused application of high mechanical index ultrasound to the heart while the patient is receiving an intravenous infusion of a microbubble contrast known as "Definity®". “Definity®" is an injectable cardiovascular ultrasound contrast agent comprised of lipid-coated echogenic microbubbles filled with octafluoropropane gas that enhances clinicians’ view of the left ventricle of the heart during an echocardiogram to aid with diagnosis. Contrast Dosage The commercially-available microbubbles (Definity®) to be utilized for these studies will be manufactured by Lantheus Medical. In each session, one vial (1.5 millilitres) will be mixed with approximately 48.5 millilitres of saline (approximately a 3% infusion) and then infused at the rate of 1~2ml/min (adjusted with image quality). The Pre-PCI infusion will last for ~3-5 minutes, while the post-PCI infusion will last for ~20 minutes. This dose and duration will be exactly the same for the intervention group and the sham echo group. The pre-Sonothrombolysis/Sham intervention will be administered as soon as the patient arrives to cath lab table prior to the PCI, and will end immediately prior to the PCI procedure commencing. Post sonothrombolysis/sham will be administered immediately after the PCI and will continue for 20 minutes. The intervention will be administered by an imaging cardiologist or a cardiology sernior registrar (advanced trainee) who is competent at delivering sonothrombolysis. All echocardiographic images for both intervention groups and sham control groups will be recorded and stored on a secure drive for further analysis. Sham Echocardiography - This sham procedure is our trial's placebo group. This group will receive a Definity contrast infusion at exactly the same rate as the interventional group for the same duration as the intervention arm. The low mechanical index ultrasound range will be <0.2 MI. Gain settings will be at 60-70% with a frame rate of 20 to 25 Hertz 1. Group 1: Pre- and Post-PCI arm Participants in this group will undergo sonothrombolysis before and after their PCI procedure. Sonothrombolysis means that these patients will receive frequent image-guided, high mechanical index (MI) (1.8 MHz; 1.1 – 1.3 MI; <5-µs pulse duration) impulses applied to the myocardial contrast-enhanced areas (using Definity®) in the apical 4-, 2-, and 3-chamber views before and after PCI. 3. Group 2: Control arm Participants in this group will undergo sham echocardiography with low mechanical index (control group) before and after their PCI procedure.


Locations(3)

Nepean Hospital - Kingswood

NSW,QLD, Australia

Gosford Hospital - Gosford

NSW,QLD, Australia

John Hunter Hospital - New Lambton

NSW,QLD, Australia

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ACTRN12620000807954


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