John Harrington M.D., a cardiologist at Scripps Memorial Hospital La Jolla in California, talks about a machine that is helping heart attack patients suffer less damage.
Interview conducted by Ivanhoe Broadcast News in March 2017.
Tell me a little bit about the clinical trial that you’re running.
Dr. Harrington: This is a research effort that’s been going on since 2002 as what’s referred to as adjunctive therapy for treatment of acute myocardial infarction heart attack. In addition to the standard approach: angiogram, angioplasty/stent of the artery causing the heart attack, (in this case the front wall of the heart) we are infusing super saturated oxygen into the artery that was responsible for the heart attack after opening the artery by balloon and stent. We infuse that with this machine for roughly an hour after the treatment for heart attack. This has demonstrated in prior trials since 2002 to be equivalent to the standard treatment for heart attacks, but to reduce the size of heart attack to a statistically significant degree, in a fashion equal to or better than the original Streptokinase / tPA thrombolytic trials, and in a fashion equal to or better than the original balloon angioplasty versus stent for myocardial infarction. This is the first real innovation we’ve had in the last ten years where we have largely focused our efforts on getting the artery open quicker once you arrive in the emergency room, or what blood clot inhibiting agents would we use during angioplasty, what have you. This is really the first new therapy I’ve seen at ten years that will potentially reduce the size of heart attacks.
When you’re talking about a heart attack are you talking about tissue that’s damaged or are you talking about actually open the artery?
Dr. Harrington: By definition, heart attack is permanent damage to the heart muscle. It does not re-grow, it does not regenerate. The sooner that you open the artery that has interrupted the blood flow to the muscle the less damage is done. I use the analogy of a house fire, the sooner you call the fire department, the sooner the fire is out, the less structural damage is done. This is a technique added onto opening the artery that will further reduce damage by improving oxygenation to the small vessels inside the heart muscle that actually supply the heart muscle. We focus our efforts on the upstream large arteries, those are the targets for bypass surgery. Those are the artery targets for balloon and stent. This is a therapy to treat the actual blood flow inside the muscle.
Have you been able to put your finger on a measurable difference that you’ve been able to make?
Dr. Harrington: In absolute terms, we have increased ejection fraction compared to the standard of care by somewhere from six to ten percent. That is better than balloon versus stent. That’s better than ‘blood clot busters’ Streptokinase versus tPA as the original treatments thirty, or forty years ago and direct angioplasty for heart attack twenty years ago. In relative risk reduction terms we’ve shown a decrease in the size of heart muscle damaged, by about twenty six percent
That’s huge.
Dr. Harrington: It is significant. We would like to see that translate to improved survival over time. A therapy that improves survival is one that we are most interested in. We have a number of surrogate end points for therapies and we hope that reduction in infarct size will ultimately translate to improvement in survival. Thus far the major improvement in survival is to open the vessel as quickly as possible. Providing the best treatment twelve hours into the event as opposed to two hours into the event is the major difference in outcome because many of our patients don’t arrive early in their event. What can we do for them after the heart attack has begun as they cross the threshold of the Emergency Room. The time to open the vessel and the method of opening the vessel is what we’ve concentrated on previous to this, but what we’re looking at here is what can be done to further improve viability of the heart muscle, and decrease the total amount of muscle damage done.
Now much more long-range because you’re looking at survivability?
Dr. Harrington: No, most of the data we have comes from three prior trials from 2002 on the AMI Hot Trial I, II, III have demonstrated that this is beneficial. This trial, the IC-Hot Trial is to modify the treatment regimen where we don’t actually leave a catheter inside the heart attack artery we’re leaving it inside the main vessel of the heart. This is a trial looking at heart attacks involving the front wall of the heart only and for people who have arrived at the emergency room within six hours of the onset. It doesn’t translate to all heart attacks just anterior MI, that is heart attack involving the front wall of the heart.
Tim France, why was he a good candidate? What have you found with his case?
Dr. Harrington: We consider anybody a good candidate who is anterior MI within six hours onset of symptoms who had not had prior angioplasty before, not had bypass surgery, not had cardiac arrest, and do not have other complicating features. That’s part of what research is about is to study a group of people that are somewhat homogeneous to make sure that the results that you get are not confounded by other variables. Because this was his first event, (never been treated before), and he arrived at the hospital within six hours, he was considered a good candidate for participation in this trial. Most importantly, he was willing to participate because you have to notify people that we believe this is beneficial but the reason that we’re doing the research is to prove that it’s beneficial. The person’s sense of altruism is what allows us to do that as a participant in a research trial. Many of the things that we do (and take for granted) now, in treating many disorders would never been done if we didn’t have people willing to volunteer to participate in research trials.
He’s been doing pretty well. He was talking about a 500 mile hike. When or does this trial have an end point and when will this be available as standard treatment?
Dr. Harrington: Well, that’s two different issues. This trial is limited to one hundred patients because statistically that’s what is felt to be necessary to prove this version of the treatment technique and it is providing further evidence of safety and efficacy to the FDA. To prove that something is an appropriate treatment you have to prove that is not only safe but it is equal to or better than the standard of care. That requires an awful lot of data for the FDA. This is an effort that’s been going on since 2002. When the FDA approves something it’s determined by many factors. The more data that you have demonstrating safety and efficacy, the hope is that yes, this will become part of our standard of care. But right now it is still considered a research protocol.
How many people do you have? How many spaces do you have left?
Dr. Harrington: I believe they are on the eighty sixth patient out of one hundred. They’re hoping to conclude the trial within the next two to three months. Recruiting people who have the right type of heart attack who present at the right timeframe, who have never had any prior treatment, we look at a large number of people but only talk to a small percentage, and then those individuals also have to be willing to participate in the trial.
Do you have the Phase III?
Dr. Harrington: This is Phase III.
No telling how quickly they will turn that around.
Dr. Harrington: The FDA looks at all things with an independent panel of experts. Many things that we thought intuitively would be a good idea for various treatments have turned out not to be after they’ve been studied in the real world. The FDA now looks at many drug therapies, or device therapies, asking the question will this show the same benefit when it’s actually released to the general public. That’s a very difficult thing to know in advance in defense of the FDA’s view of the world.
What’s your observation with what the super saturated OT?
Dr. Harrington: In some respects it’s forest for the trees because we’re seeing a small percentage of the patients that we’re working with and you always interpret your patients outcomes and your results, subjectively; it’s very difficult to be objective. You’re dealing with people and their health concerns and that’s one of the issues. If you say, well, in my series of patients this has done well. I’m going to recommend this to other patients, there’s a certain amount of personal bias in that. That’s exactly what research is intended to overcome is patient selection bias, personal bias, outcome bias. The really only way to know that something is effective is to have a large number of people and very defined endpoints. All too often we discover that the endpoint that we wanted was perhaps not the best endpoint or the surrogate marker we’re using is perhaps not the best. That’s why you hear varying results of research trials in the news. This is good for you, that’s not good for you, coffees good, red meat is bad, for example, you hear conflicting results because it’s an ongoing effort to define what actually is beneficial and what is not beneficial.
What haven’t I asked you about the super saturated trials, that you think that we should put in the story?
Dr. Harrington: I would emphasize that the people who participate in these trials as volunteers are really the most important part of what we’re doing. Getting people to agree to volunteer for something, as they are in the middle of their own health crisis, is not easy for anyone. They have lots of concerns to review in addition to what we’re discussing with them about their heart attack.
END OF INTERVIEW
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