RCT: Azelastine Nasal Spray Reduces COVID by 67%

What is discussed, and when

1. 0:00 – 5:00: MedCram
2. 10:00 – 15:00: AstaPro
3. 20:00 – 21:35: MedCram

Notable quotes from "RCT: Azelastine Nasal Spray Reduces COVID by 67%"

• Welcome to another MedCram video. It's been a while since we did a COVID 19 update, but I think it's time based on this randomized clinical trial that was published in JAMAMA in September of 2025.

  about MedCram · at 0:02

• Taken this prescription nasal spray and made a over-the-counter version called Astapro, which is sweeter and it actually is stronger. Instead of 0.1%, it's 0.15%.

  about AstaPro · at 14:10

Who and what is mentioned in this episode?

Companies & orgs

• MedCram — Company · 3 mentions · first at 0:02
• JAMA — Company · 1 mention

Products & tech

• Azelastine — Product · 5 mentions
• AstaPro — Product · 1 mention · first at 14:16

Concepts & topics

• SARS-CoV-2 — Concept · 3 mentions

Full transcript with timestamps

0:00 medcra.com. Welcome to another MedCram video. It's been a while since we did a COVID 19 update, but I think it's time based on this randomized clinical trial that was published in JAMAMA in September of 2025 looking at a zealistine nasal spray for the prevention of SARS KV2 infections. This is pretty interesting study. We're going to get into this, but first I wanted to talk to you about medcram.com. If you are a healthcare provider or if you're just interested in medical videos, join us at medcram.com for the latest in medical education and continuing education units. Medicine explained clearly. MedCram.com.

0:43 So, let's get back to this idea that a antihistamine nasal spray can actually prevent COVID 19 infections with SARS KV2. This was a paper that was published in January of 2021 titled identification of antiviral antihistamines for COVID 19 repurposing. And basically at the time people were looking at different shapes of molecules and how they could fit into the A2 receptor which was seen at the time and is true as the receptor for the SARS KV2 spike protein. And this is what they found. I will give a link to this paper in the description below. But as you can see here, this is the crystal structure of the human sigma 1 receptor bound to a lian that was used as the basis for molecular docking with autodock vena. This is a liand. And what they found was that the molecular docking here predicts binding of dyen hydramine or benadryil and aelastine to the lian binding pocket of the sigma 1 receptor. And this is one of those

1:48 receptors that is associated with the binding receptor where SARS KV2 enters into the cell. So people were looking at this and actually testing it and lo and behold in vitro there was some activity as well as other molecules specifically with this antihistamine molecule aelistine that actually had some efficacy in vitro. But it's one thing to have efficacy in vitro and quite another thing to actually see that efficacy in randomized control trials. Just a couple of years ago, there was another paper that was published. And of course, there's other papers that were published that we're not going to cover here. This one was early intervention with a zealistine nasal spray may reduce viral load in SARS KV2 infected patients. So, this is people that were already infected and they divided them into three groups. Those that got placebo, those that got 0.02% and those that got 0.1% a zealistine. Now, this is important

2:45 because this, as it turns out, is going to be the strength that we're going to see in our study today. And they took it for 11 days. So, these were people that were not negative and wanted to see whether it would prevent infection. These were people that were already infected to see whether or not the viral loads as assessed by quantitative PCR would actually get better. And what they found was is that it actually did, especially in the highest dose there of the 0.1%. entered this phase 2 randomized clinical trial looking to see whether or not it would actually have the same benefits. A zealous nasal spray for prevention of SARS KV2 infections. Here we're going to be looking at people who have not been infected who just start taking this nasal spray and to see whether or not you can prevent getting COVID in the first place.

3:35 This is called the contain trial. Let's take a look at some of the features. This is a phase 2 doubleb blinded placeboc controlled 450 volunteers and this is in Germany. These are people that are 18 to 65 years of age. They're healthy. They're actually been shown to be negative for SARS KV2 at the beginning of the trial. If they're already using antihistamine or nasal product use or they're pregnant or breastfeeding, they were excluded. And what they did was a onetoone randomized control trial where they put people on either the 0.1% nasal spray or placebo.

4:07 Now, it's not clear exactly which placebo it was. I think it's probably going to be some sort of inert substance. This will become important slightly because there are other inactive and active substances that are in this aine nasal spray. And the question is whether or not they're actually an active ingredient or not. We'll talk about that in a little bit. This was centrally located and it was double blinded and the intervention was routine which was one puff per nostril three times daily. Normally it's two times daily, but here they did it three times daily for 56 days. Now, I say that normally it's two times daily because this medication, which is the prescription strength, which ironically is actually lower in strength than the one that you can get over the counter.

4:51 It's the 0.1% nasal spray. This is actually used twice a day for people who have allergic rhinitis. In this case though, they did it three times a day and they did it for 56 days. If they felt like they were having symptoms or they confirmed an exposure to somebody else that had CO 19, then they did it for five times a day for three days. Twice a week they would have these rapid antigen tests to see whether or not they were positive because that was easier to do, less expensive. And if any of those turn positive, then they would confirm it with a PCR. The question is is what's the difference between the intervention group and the placebo group? is is it possible that antigens here in this nasal spray might be triggering some of these? Well, I would say that the chances of a false positive are pretty low because they're all going to be confirmed by PCR testing. So, if there was something either in the placebo or

5:45 in the treatment group that would have triggered this either one way or the other, it would have been fine-tuned out because it would not have turned a PCR test positive. If they were symptomatic and they were rat negative, then they did a multiplex. That's where they do a whole battery of tests to check for things like the flu, enrovirus, etc., etc. They also check for symptoms and adverse events. Those are AEES. So, what was the end point? Who actually got infected by day 56? And the secondary end points were were there symptomatic infections, time to infection, duration of positivity, and other things. And then, of course, safety. So, let's take a look at some of the data here. Here were the primary and secondary outcomes of a zealistine therapy for pre-exposure prophylaxis. Here is the intervention group. Again, this is the 0.1% group and this is the placebo. And of course, this is the difference with the

6:37 95% confidence intervals. So, what did they see? They saw that out of 227 in this group, only five or 2.2% got infected. Whereas in the placebo group, 15 or 6.7% got infected. That's an odds ratio of.31. That means that if you were in the intervention group, you had a 69% less odds ratio of getting infected. We're going to go through those numbers here in just a second. What about symptomatic SARS? It was 4 and 14, about the same as 5 and 15. The time to SARS infection was actually much longer in the intervention group than it was here.

7:15 And you can see here what the distribution was. And what about the duration of rat positivity? Well, it was less when you were on the Azelistine, which is sort of commensurate with what we saw on the previous examinations. What about secondary end points in terms of overall infections? You can see more infections in the placebo group. Participants with greater than one laboratory confirmed infection, greater again. And then self-reported days of illness was greater in the placebo group. Let's actually go through and calculate some meaningful numbers here.

7:46 Let's make a table, which I always like to do. What we have here are those that have disease and those that don't have disease. Those that were being treated with the nasal spray and those that were not being treated. How many were treated that got the disease? There were five. How many were treated that did not get the disease? There were 222 making a total of 227. And how about those that had disease that were not getting the actual intervention nasal spray? There was 15 of those. And this was 208. and this was 223.

8:18 We need to look at how many with disease out of the whole group. So this would be 5 / 227 otherwise known as the treatment event rate. The treatment event rate is 5 / 227. This is the total here. What about the control event rate? Well, that's just going to be 15 / 223. Okay. So 5 / 227 is 0.022203. Or another way of saying that is 2.20%. 15 / 223 is 0.06726 which is about 6.73%. So the control event rate was 6.73. The treatment event rate was 2.20. So what we want to do is figure out what was the relative risk reduction. In other words, if you were to take the nasal spray, how much could you decrease your infection rate by? And to get that, we simply take 6.73, subtract 2.20, and divide it by our denominator, which is 6.73. And what we get there is actually 67.3%.

9:39 So taking this nasal spray can actually reduce your chances of getting SARS KV2 infections by 67.3%. Let's look at the absolute risk reduction. Now to do that it's simply 6.73 minus 2.20 which is going to give us 4.53%. This means that if I were to give everybody in the population a nasal spray, I would be able to reduce the chances of anybody in the population getting that disease by 4.53%. This is the difference between the relative risk reduction and the absolute risk reduction. The relative risk reduction is probably a better measurement of the efficacy of this intervention. And the reason is is because the particular endpoint that we're looking at here is an infectious disease that can actually fluctuate very greatly. The thing that you need to know is the absolute risk reduction is extremely dependent on the prevalence of the disease in the population. This 4.53% absolute risk reduction is only

10:48 correct at this particular time with this prevalence in the population. If the prevalence of SARS KV2 goes up significantly, if there's a surge, these numbers here are going to go up very high. If these numbers go up high, the difference between this is going to be very, very high. And therefore, the absolute risk reduction is also going to go up very high. The nice thing about relative risk reduction is that this relative risk reduction does not change regardless of what the prevalence is in the disease population. And that's the reason why I like to go with the relative risk reduction when we're talking about a disease that can change in the prevalence. If we're talking about coronary artery disease, things that don't change dramatically in terms of prevalence, then I would prefer the absolute risk reduction. It's a little bit more robust. But if you're talking about a disease which fluctuates widely,

11:39 then the absolute risk reduction doesn't have a lot of validity outside of the prevalent situation in this particular study. However, you can take the relative risk reduction very easily. So, there's actually a video that we put together that talks about this more if you're interested and specifically about CO 19 vaccines and the absolute risk reduction in those and why it's different than the relative risk reduction and which is the one that you should use depending on what it is that you're looking for. How do you calculate then the number needed to treat? In other words, what is the number of people that you need to give this prescription out to to prevent one person from developing COVID 19? And it's simply 1 over the absolute risk reduction. So in this case, it's 1 over 0.0453, which as it turns out is about 22.08, but we always round up with the number needed to treat. So the actual the

12:32 number here is 23. That means you would have to give out 23 prescriptions to people in 56 days to prevent one COVID 19 infection. Now realize that that's with the current published absolute risk reduction. If the prevalence of the disease were to go up hugely, then this thing would absolutely change. This absolute risk reduction would go up dramatically, which means that the reciprocal of it would cause this 23 to probably drop to something lower. Obviously, maybe 15 or even 10 or even lower than that. If the disease is prevalent in the population, the number needed to treat is going to be much lower. So I hope that's helpful in terms of the statistics with regards to using this nasal spray. And you can see here over time how this got better and better and better with the zealistine here at the bottom in terms of the cumulative infection rate and placebo up here at the top. We've talked about the

13:26 efficacy. Let's talk about the safety. When we look at adverse events, we can see that there was actually more adverse events in the placebo group than there was in the intervention group. And that might be because of the amount of COVID that was going on in the placebo group. However, if we look at related adverse events like things having to do with the nose, we saw that there was more in the intervention group. Participants with greater than one adverse event was about the same. Greater than one related adverse event was higher in the intervention group than it was in the placebo group. And you can see the rest of these things. What were some of the side effects that we saw? Adverse events for the aelastine compared to placebo.

14:04 We saw that bitter taste was one of those side effects. We're going to talk about this in a little bit. They have taken this prescription nasal spray and made a over-the-counter version called Astapro, which is sweeter and it actually is stronger. Instead of 0.1%, it's 0.15%. And instead of having to take it twice a day as a prescription, you can take it once a day because it is a higher strength. And as a result of that, we see much less bitter taste in the over-the-counter version of this prescription medication. But realize that in this study, they use the prescription medication. And they also noticed here that nose bleeds was significantly higher. There was tiredness, headaches, and Hashimoto thyroidis.

14:50 They did not feel that that was actually related to the nasal spray. It was just by chance any treatment related AE it was 26.9% versus 11.2. So there are some definite side effects with this formulation. Let's look and see what's actually in it. The active ingredient is aine hydrochloride. Some points to think about here is this is an anti-histamine. Things like benadryil and traditional antihistamines also have anticolinergics. And so that is important to understand because chronic use of antihistamines have actually been implicated in Alzheimer's disease. Aelistine the nasal spray is actually less anticolinergic than benadryil does not cross the blood brain barrier. Nevertheless, there have not been long-term studies on aelastine.

15:36 What are some of the other quote inactive ingredients that is packaged with aine when you pick it up from the store? There is an additive is supposed to keep bacteria and viruses out of that solution. so you don't spread it around when you're storing it. And it's this benzylconium chloride. The question is is whether or not this is the thing that's actually doing the heavy lifting with this study. It could be, but one of the reasons why I think it may not be is because we see this in a lot of different nasal sprays, even steroid nasal sprays. And there's actually been studies that have shown that the use of steroid nasal sprays in CO 19 was a wash. There were some studies that showed that there was a slight benefit, some studies that showed that there wasn't. If this was actually doing what it was supposed to be doing, I would have expected those studies to show a benefit in those nasal sprays where it

16:24 actually is used. Couple of other things here that I don't think would be very beneficial and I think those are more for preservative. Let's talk a little bit about the use of this. So, practically speaking, if you wanted to use this nasal spray, you would need to get a prescription from your doctor to get it. The good news is is that this very same medication is available over-the-counter in a higher strength and one that is given once a day. Let's look at this. The prescription for a zealistine which is 0.10% originally branded as Aelin not a pro but ain was FDA approved back in 1996 at 137 micrograms per spray designed for twice daily use to balance efficacy and safety in treating allergic rhinitis.

17:09 Asta Pro evolved from this in 2008. It reformulated the 0.10% version with taste masking agents like sucralose. Remember we told you that one of the big side effects of the prescription aelastine was its bitter taste. In 2009 a higher 0.15% strength, so one and a half times the strength which was 205.5 micrograms per spray. APro was approved. This is once daily dosing for improved compliance and 24-hour relief. At that point, it was actually so safe that it was given OTC approval because of this and also customer demand. However, the 010% just by legacy is still prescription only. This is why it doesn't make any sense that the lower strength requires a prescription and the higher strength doesn't. It's not for any other particular reason. It's just for legacy reasons. The over-the-counter is not weaker. It's actually stronger. It's once a day and it is better tolerated because they've added some sweetness to

18:16 it so that when it goes down, it's not so bad. Let's take a look at the two that are available right now. This is the prescription. I'm going to put an RX here. And up here, I'm going to put OTC just like it says right there. So, the concentration for the over- the-counter is actually one and a half times what it is for the prescription. The availability, it's over-thecounter. This is prescription only. But this is the one that was actually used in the study three times a day. What would you have to use here to get that? You probably have to use the over-the-counter dose probably two times a day. That would get you up to about the same concentration.

18:49 The overthec counter is for adults and children as was the prescription. Here they usually do two sprays per nostril once daily. And here they would do one to two sprays twice daily. So you can kind of see what you would need to do there if you wanted to prevent CO 19. In terms of the indications, they're pretty similar. In terms of the taste profile, there are very different. Remember, we said there was a more bitter taste with the prescription and more of an improved formulation, sweeter with the over- the-counter where only 3 to 6% of users will actually have that bitter taste.

19:21 Side effects, the bitter taste is only up to 6% whereas over the counter it's up to 20%. Something that may actually make a difference for you, especially if the bitter taste is an issue. In terms of effectiveness and onset, the over-the-counter can start working in as little as 30 minutes. There is no real timing on the prescription. There is a similar effectiveness for allergies, but the onset duration is tied to the twice daily dosing. What about the cost? The over- the-counter is actually more expensive at 20 to $30 for a 200 spray bottle. If you can get a prescription and get the generic prescription for it, your prescription plans will often make it as low as $10 to $20. So you can make a decision there. So what they believe is going on here is that the anti-histamine molecule a zealistine is actually blocking the ability of the SARS KV2 virus to bind the A2 receptor and as a result of that it's reducing

20:16 its ability to cause infection. And it brings up a good question when should we use this? I think it might be beneficial if you're going into high-risk situations. If you're going into a crowd, if you're flying, there's been some sort of exposure, it might work in that kind of a situation. It seems to reduce at least the time that you're positive. Should you go on this indefinitely? I don't think for this indication it would be a good idea. We don't have a lot of long-term studies. There are people with allergic rhinitis, however, that do take this on a regular basis. It would be interesting to see those people from a historical observational standpoint whether or not they were less likely to get SARS KV2 infections in CO 19, but I think that more research is needed in the long-term effects.

21:00 I hope you enjoyed this video and bringing this to your attention. It's been really busy. Hopefully, we can get some more videos up and we'll talk a little bit more about light and some infrared light photography that I've been playing with. If you've enjoyed this, please subscribe, turn on notifications, leave us a comment, tell us what you think, and join us at medcram.com for more continuing medical education and medicine explained clearly. Thanks for joining us.

Questions about this episode

What is discussed in "RCT: Azelastine Nasal Spray Reduces COVID by 67%"?

In order: 0:00 MedCram; 10:00 AstaPro; 20:00 MedCram.

What is mentioned in this MedCram - Medical Lectures Explained CLEARLY episode?

5 people, works and ideas are mentioned, including Azelastine, MedCram, SARS-CoV-2, AstaPro, JAMA. Each one on this page links to its own page with every episode that mentions it.

How long is "RCT: Azelastine Nasal Spray Reduces COVID by 67%"?

The episode runs 22 min; the transcript is about 3,703 words in 27 timestamped sections.

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