The pre-specified composite endpoint that included both moderate and severe bleeding events demonstrated a win ratio of 1.33. And for the audience, let me remind you that any win ratio above 1 suggests a treatment effect for the investigation in the device. However, that win ratio was not significant with a p-value of 0.202. The pre-specified composite endpoint that only included severe bleeding events demonstrated a win ratio of 1.59, which was significant with a p-value of 0.041. Since the [indiscernible] definition allows for events to be declared simply by transfusions, the principal investigators of the study wanted to ensure that only clinical bleeding events were included in the analysis and therefore performed a sensitivity-blinded review of the event where they identified a number of cases that were included in the original analysis simply on the basis of transfusions but without any evidence of clinical bleeding.
The results of the sensitivity analysis as shown at the bottom of the table were now the composite endpoint that includes the moderate or severe bleeding events has a win ratio of 1.65, which is also significant with a p-value of 0.026. You will note that the composite that only includes severe events was not impacted by the sensitivity analysis, since all severe events were deemed to be clinically meaningful events relating to significant bleeding. Finally, the exploratory major bleeding analysis looked at the total of major events that these subjects suffered either according to the UTBB definition or according to chest tube drainage by accounting for patients that ended up with more than 1 liter of blood in the chest tubes that are placed in the chest after surgery.
What we saw that there were three major UTBB events in the drug zone bar while there were nine in the control arm. And when it comes to major chest tube drainage bleeds over a liter, there were none of those noted in the drug zone bar there were four additional in the control arm for a total of three events with drug-absorbed and 13 in the control arm. That translated to rates of 6% versus 22% between the two arms, which was significant with a p-value of 0.028. The number needed to treat to prevent the major bleed in the trial, according to this exploratory analysis, was six. Otherwise said, for every six patients treated, there was one major bleeding event averted. Next slide, please. With STAR-T data available, we have worked closely with both internal and external regulatory experts to formulate a regulatory strategy leading up to submissions.
Included on the top of this slide is a direct quote from one of our senior regulatory experts, Mr. Mark DuVal, J.D., President and CEO of DuVal & Associates. We have been working with Cytosorbents on the development of the regulatory strategy for the DrugSorb-ATR device. Based on the data the company has shared with us and the extensive experience we have in preparation of de novo submissions, it is our opinion this device is appropriate for the de novo pathway. More specifically, the de novo pathway is for low to moderate risk devices for which special controls, for example the availability of clinical data, provide reasonable assurance of safety and effectiveness, but there is no other approved predicate device. The de novo pathway puts heavy emphasis on the probable benefit and risk of the device in the intended population.
Importantly, based on the priority review received by breakthrough devices, a recent analysis reported a 25% faster de novo application review time. Accordingly, we will be proceeding with parallel FDA de novo and health cannabis admissions in the third quarter of this year. And finally, FDA review times for de novo applications are stated as 150 days. However, in the post-COVID era, such reviews are averaging approximately 1 year Next slide, please. So, to summarize, ticagrelor is an FDA-approved drug that’s widely used as standard of care in the U.S. and Canada, but does confer an increased risk of severe perioperative bleeding for patients who require urgent surgical treatment. DrugSorb-ATR is an investigational device that has FDA breakthrough status for this application, highlighting the large unmet medical needs and the lack of available alternatives.
We believe that the STAR-T data inform the regulatory pathway by providing the necessary safety information, information on the proposed target intended population, which in our case will be CABG surgery, and information the proposed indication for use, which would be for the reduction of bleeding severity. Based on the benefit to risk profile observed in STAR-T, regulatory experts recommend FDA submission for drugs DrugSorb-ATR use in CABG surgery under the de novo pathway. And finally, pending FDA agreement of the de novo pathway, breakthrough designation status is expected to facilitate a priority review with a potential FDA decision between 6 to 12 months following a Q3 submission. In parallel, we’ll be also submitting to Health Canada.
And that concludes my prepared statements, and now I’d like to turn it over back to Phil for his concluding remarks.
Phil Chan: Thank you, Makis. We see tremendous opportunity fueled by important demographic trends, such as the aging baby boomer generation who are prone to critical illness, expanding global use of blood thinners by millions of people all over the world for stroke and heart attack prophylaxis, and the chronic liver disease epidemic in 20% of the world population due to alcoholism, hepatitis, and fatty liver. We are at the forefront in helping to fill the substantial treatment gaps that exist across a spectrum of critical conditions such as sepsis, shock, liver failure, acute respiratory distress syndrome, infective endocarditis, serious bleeding due to blood thinners, and organ transplant because of our ability to help control deadly inflammation and remove dangerous toxins and drugs that are often at the heart of life-threatening conditions.
And in the future, with products in advanced development like HemoDefend-BGA for universal plasma, our contribution could be even greater. We are excited by our near-term progress with sales, product gross margin, potential catalysts like PuriFi, our strategic partnerships like Fresenius, our goal to obtain debt financing, new clinical data, and importantly, the greatly increased visibility that we all now have on DrugSorb-ATR. By continually pushing boundaries and driving innovation, we are committed to expanding the dimension of blood purification, setting the stage for lasting transformation within the industry. And with that, this concludes our prepared remarks. So, operator, please open the call up for the Q&A session.
Operator: Thank you. [Operator Instructions] Questions now come in from the line of Yuan Zhi with B. Riley Securities. Please go ahead.
Yuan Zhi: Thank you for hosting the Q1 call. I have a couple of questions here. I am curious about the decision to pursue this de novo application versus pre-market approval, what has changed since the last discussion?
Phil Chan: Yes, thanks, Yuan. Maybe let me turn that over to Makis to discuss. Makis?
Makis Deliargyris: Yes, thank you for the question. The simple answer is the availability of the STAR-T data that we believe are very informative when deciding what the appropriate regulatory pathway is. And as reviewed on the slides that we just look at, the de novo pathway is specifically designed for devices of low to moderate risk, which again the STAR-T data provides a lot of visibility around that component as well in addition, obviously, to the efficacy result. So that was the main determinant in addition to of course input from both our internal regulatory resources and of course external regulatory experts.
Yuan Zhi: Got it. And then another follow-up here is for the targeted submission in 3Q, I am curious have you guys talked to FDA for this pre-submission? And what’s your confidence to have this submission on time as you are preparing the data package and the minutes after the FDA meeting?
Makis Deliargyris: So we are – as you know, the trial completed last year in 2023. So we have used the last few months, obviously, in doing a lot of the necessary work requiring on closing, cleaning and analyzing the data. That’s culminated in the presentation, obviously, a double ATS. So there has been a lot of work along the way to get ready for these submissions. And we are now entering the final phase, which is preparing the documents now that the regulatory pathway is more clear to have the exact necessary materials for the submissions. Our FDA interactions have always been starting with the breakthrough designation applications have always been very collaborative and very productive. So we anticipate and hope that they continue that way now that we have also the STAR-T data available that will be a centerpiece of the submission.
Yuan Zhi: Maybe another clarification question here is before you submit this de novo application, is FDA requiring a pre-submission meeting to make sure everything is in line with their expectation? Thank you.
Makis Deliargyris: It is our understanding based on the discussions with our regulatory experts that the pre-submission meeting is not required by the FDA.
Yuan Zhi: Got it. That’s all we have. I will hop back on the queue.
Operator: Your next question now comes in from the line of Sean Lee with H.C. Wainwright. Please go ahead.
Sean Lee: Hey, good afternoon, guys and thanks for taking my questions. I just have two of them. First is on the good product sales we saw this quarter. So, could you highlight what exactly were the pushes and pulls that helped you achieve the $9 million?
Phil Chan: Christian, would you like to answer that?
Christian Steiner: Yes, sure. Thank you for the question and good evening from Berlin, Germany. Yes, we had a very positive development in the first quarter in sales and as discussed at the last earnings meeting, there is a very positive development, especially in the direct sales in Europe and in many of the distributor countries. We still see the market challenges in the Central European countries like Germany, Austria, Switzerland, they have stabilized and we think the market stabilizes so that we can develop from here. But the major push as I have said come from the direct sales in Europe and this distributor countries.
