Will Vitamin C and Zinc help your COVID symptoms?

Podcast Transcript

Announcer:
Welcome to Love Your Heart, brought to you by Cleveland Clinic's Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute. These podcasts will help you learn more about your heart, thoracic and vascular systems, ways to stay healthy and information about diseases and treatment options. Enjoy.

Dr. Milind Desai:
Hello everybody. I'm Milind Desai, and I am a cardiologist at the Heart and Vascular, Thoracic Institute at the Cleveland Clinic. And I would like to share the results of a study that we have recently published. This is in the space of COVID pandemic that we are all dealing with.

Dr. Milind Desai:
And it is my tremendous honor and privilege to discuss the results on behalf of my colleagues and co-authors. I would specifically like to thank my co-authors, Dr. Suma Thomas, Dr. Nissen, Kathy Wolski. Ms. Wang, Dr. Div Patel, Dr. Kumar, Dr. Il’Giovine, Dr. McWilliams, Mehra, and my research coordinator, Barb Bittell, who helped tremendously with the study.

Dr. Milind Desai:
So as all of us have been dealing with the majority of 2020, the pandemic, it has created a havoc in our lives. Lots of lost work days, lots of sick patients, lots of dead patients, unfortunately. So the study involved... What we wanted to study is patients who are not symptomatic enough to be in the hospital, meaning outpatients, how would some therapies that have plausible biologic effects impact their disease duration and the symptom scores, et cetera.

Dr. Milind Desai:
So let me walk you through what we did. Early on in the pandemic, like March or April of 2020, we were beginning to recognize that this is rapidly spreading. And majority of the patients do not need hospitalization, but they are symptomatic and can be treated at home. So the question we had was, what are some of the therapies, especially over the counter therapies, that can be used to help with these patients to reduce their disease burden.

Dr. Milind Desai:
As many of us have read and follow, there is some literature in terms of zinc as well as ascorbic acid or vitamin C in reducing, or at least reducing the rate of common cold, the common viral infection that we often see. And this is a multi-billion dollar industry in the United States where patients or subjects that are affected by this, they take these over the counter.

Dr. Milind Desai:
Now, the data related to this is not as robust. The utility of this has not been demonstrated in a rigorously studied prior publications. So that was what we wanted to look at, at the outset. So what we did was design this randomized controlled trial where we divided the patients into four groups. The first group would be standard of care. The second group was zinc at 50 milligrams. The third group was ascorbic acid, or vitamin C at eight grams, spread over multiple times a day with meals. And the fourth group combined zinc and ascorbic acid at the doses that we talked about.

Dr. Milind Desai:
The original plan was to study a little over 500 patients, divided into these four groups. The primary end point that we wanted to study, it was a novel endpoint that we develop. It was based on a four symptom score. The four symptoms were developed based on the CDC guidelines at the time, which involved fever, cough, fatigue, and shortness of breath. And the score was developed based on a score of zero to three, zero being no symptoms and three being severe symptoms. And so the maximum a patient would get would be 12. The minimum would be zero. So the primary endpoint was how many days does it take for the symptom score to get to 50% from where they started? So in short, the patient would act as their own control, for the lack of a better term. That was the primary endpoint.

Dr. Milind Desai:
The secondary endpoint was how many days does it take the patient to get to a score of zero, hospitalizations, deaths, et cetera? Obviously, I will say this study was not powered to study death in all this.

Dr. Milind Desai:
So the huge thing about this study was how quickly we came up with the idea, ramped it up during the extremely challenging times earlier in the pandemic when the entire health system was shut down, research was shut down. So we had to innovate and adapt the various processes that we take for granted in terms of doing research, including keeping the coordinator safe, keeping all the distance between the patients and the coordinators. How do we get informed consent? How do we deliver the drugs to them? How do the patients monitor their symptoms? So it involved a lot of teamwork across multiple disciplines, including cardiology, respiratory Institute. We involved sites all over the Cleveland Clinic facilities in Northeast, Ohio, as well as our Florida Weston facility.

Dr. Milind Desai:
So that was a huge endeavor at the time to make it happen, and make it happen adapt in real time, and do it quickly before things got completely out of hand. So that was one of the first things, the biggest challenges. So what we found sometime in October... So the study got started towards the end of April. Sometime in October, middle of October, we decided to do an interim analysis on 214 patients to see where we are, where we stand, and whether or not this idea is going to bear fruit.

Dr. Milind Desai:
So at the end of the day, what we found in October, we had recruited 214 patients across relatively well distributed across all four groups. What we found was the primary endpoint of reducing the symptom score by 50% did not achieve statistical significance. So across the standard of care group as well as all the other groups, it was not any different. There was no difference in also any of the secondary endpoints. About 10% of the patients reported significant side effects, mostly in the ascorbic acid or the vitamin C group. And three patients died due to exacerbation of COVID related symptoms.

Dr. Milind Desai:
So obviously, because of low conditional power for achieving statistical significance, we decided as a... Our OSMB met and decided to stop the trial in October. And so the results that we are presenting are from a prematurely terminated trial of 214 patients.

Dr. Milind Desai:
So basically, what are some of the takeaway points from this study is, teamwork. We were able to muster up a team across multiple disciplines, as I alluded to, in real time, during incredibly challenging circumstances of the pandemic. We learned a lot. We innovated a lot. We adapted a lot. So teamwork, as I alluded to, was crucial.

Dr. Milind Desai:
The second, necessity is the mother of invention, and to operationalize a trial like this was challenging, but we were able to do it.

Dr. Milind Desai:
The third crucial thing is, a lot of things make biologic and plausible sense. We like to do things just the way our grandparents used to do this. Today, over the counter recipes, over the counter regimens, are a multi-billion industry. And a lot of these recommendations are based on no real substantive data. This is now a randomized controlled trial which suggests, at least in the COVID population, that this concoction does not really work. It did not achieve primary or secondary endpoint.

Dr. Milind Desai:
And the last thing I want to say is, a trial of this magnitude to develop, and execute a trial like this, cost money. And I'm incredibly grateful to the Cleveland Clinic leadership for providing the resources, the human personnel, as well as the money aspect of it, the financial aspect of it. This study was conducted entirely out of Cleveland Clinic internal funds that were generated out of Philanthropy Institute, basically for the sole purpose of doing COVID research. So an important message was learned from this negative trial about how to operationalize something complex, how to do it fast, adapt in real time, and you know how to do it effectively with non-traditional modes of financing.

Dr. Milind Desai:
If you are a patient, what are the key takeaways from this study? Sometimes you have to question what we have been doing, and does it make sense to continue taking some of these medications? Clearly, the study demonstrates that the combination of zinc and vitamin C does not help reduce symptoms score. But, as a patient, you still need to continue to do the right things, the social distancing, wearing a mask, staying healthy, and talking to your doctor if you develop symptoms that you think may be due to COVID-19. And essentially, that is the bottom line as it relates to this disease.

Dr. Milind Desai:
Thank you.

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