Looked into $ICU. As far as YOLO plays go, this seems somewhat lower risk, having been peds approved already. Adults don’t quite bounce back as well, but at a super low market cap, might be worth dabbling.
What are thoughts on being diluted into oblivion? They only have enough cash for 2ish more quarters. Seems like the best hope (and most likely) is a buyout, which could still be a 10x or more from here. Seems like an interesting binary play of either going to zero or the moon, but less risky than most other moonshots out there.
still havent researched this a ton, but here is feedback i got from a fellow ESPR investor who told me about ICU. This person works in medical industry.
Generally agree- hugely binary. Question is if dilution is going to wreck this before it gets started. Really to me this is about ICU having finances to not have to be sold for pennies on the dollar because they can’t afford to scale up. Also, renal world already has an example of a stalled / failed device- see outset medical.
Side note, I disagree with stopping a trial early. Big red flag. You design a trial to detect a small difference beyond a reasonable doubt and base your N off that. If you stop early, you still keep a reasonable doubt there. You do it to “strike while the kettle is hot” and not run the chance of regressing to the mean. The evidence based wonks will be highly skeptical is this happens.
Keep in mind sepsis is a highly heterogeneous patient group, so you probably need alot more patients than what they’re actually trialing. If this is stopped early, I can guarantee there will be alot of doubters. Example of a potential argument, “the intervention arm had more strep infections and more pneumonia and we know those patient populations tend to do better” …. This data is going to get wildly thin sliced.
Add to it hospitals don’t really have spare cash to throw around nowadays. We’re just trying to get by.
Xigris, EPO, and the CAST trial are all examples of “we jumped too early and hurt people” …. Honestly probably sarepta too.
So I was still intrigued…. Then found cytosorb (CTSO) does the same thing, more work less, and is already approved. Sadly, I’m going to back away from this one now.
Noone stops a trial for a small difference. Only if it is providing a big difference in outcomes with benefit beyond doubt where it becomes it becomes unethical to provide a placebo or clearly lesser treatment in the other arms of the study. Then you offer them the clearly superior treatment/intervention. This rarely happens.
These were changes implemented after the tuskagee study. Where even after the understanding that penicillin would cure the disease, many participants were told they were reviewing medical care but did not receive the antibiotics and were just followed.
Tuskegee Syphilis Study was a U.S. Public Health Service experiment from 1932 to 1972 that observed the natural progression of untreated syphilis in 600 impoverished African-American men in Alabama. The men were deceived into believing they were receiving free medical care but were denied treatment, even after penicillin became a widely available cure. The study was exposed in 1972, leading to a formal apology from President Clinton in 1997 and significant reforms in research ethics, including the establishment of the National Center for Bioethics in Research and Health Care at Tuskegee University.
This is taught in every medical ethics class across the country
Happens quite frequently, and has happened quite a bit since the Tuskegee experiment (which honestly seems minimally relevant here) This isn’t interventional cardiology where the newest inventions get picked up quickly with minimal skepticism and often overwhelming (& probably irrational) hope/hype. The medical critical care is a highly skeptical bunch. And the other group that holds the keys here- nephrology- is also pretty slow to adapt to new changes (given many still believe contrast nephropathy still exists). Culturally, medical critcare and nephro are slower to adapt to new interventions (or at least for devices for critcare)
Also, clinical trials aren’t cheap, why risk extending a trial and losing potential profits?. Im not naive enough to think companies exist for purely altruistic reasons. This happens alot in various forms (exploratory analysis, changing trial endpoints, surrogate endpoints, etc) but bottom line, trials are rarely stopped early because there was overwhelming benefit, moreso they didn’t want to waste 6 months of offpatent time and wanted to get to market quickly. Id bet if you did a fragility index on trials stopped early they’re mostly <5.
Do as you all wish. The backlash here is giving nektar on Saul vibes.
A systematic review covering randomized controlled trials (RCTs) in high-impact journals (1990–2004) found that trials stopped early for benefit rose from 0.5% (1990–1994) to 1.2% (2000–2004) of all RCTs published in those journals .
Separately, in an analysis of 574 discontinued trials, 5.2% were halted specifically due to efficacy—i.e., because results looked promising—while recruitment failure accounted for about 5.7% .
In oncology, a study from 2023 found that only **1.7% of trials were terminated early due to early evidence of efficacy (benefit)** .
So certainly doesn’t happen “quite frequently”.. even in the oncology world
Trials stopped early for benefit? Not so fast!
Alan C Heffner 1, Eric B Milbrandt 2, Ramesh Venkataraman 2
While 73% of trials had planned at least one interim analysis, of those that stopped- “80% were not stopped based on formal interim analysis or stopping rule.” - they’re stopped on vibes.
Over a third of trials were unclear or didn’t state when interim analysis would be carried out…. Again, vibes.
Even in their discussion….
“ observed effect sizes in a sample of trials were much smaller than their corresponding target effect sizes. On the other hand if investigators feel that the original design and protocol remain valid, then they might conclude that the disappointing early results at the interim analysis are expected to be counterbalanced by more favorable experience in future patients.” — if the same happened for positive results, they could stop early for concern of being counterbalanced by less favorable results.
“We found that documentation of the stopping rule or decision-making processes was often missing or vague”.
Documented and detailed decision making for stopping is uncommon and probably intentionally opaque.
The original data set was meant to be 200 pts, they increased to >300.
The rosy outlook would be, “there might be some signal of benefit (but not statistically significant with just 200 pts), so let’s add more patients to see if we can tease out a small victory.”
The stages of clinical trial stoppage:
Stop early for futility.
Stop early for overwhelming benefit.
Continue as scheduled.
Continue as scheduled with MORE patients. - you are here, and this is probably just short of stop early for futility.
They didn’t get the home run they were hoping for, but still have some hope of squeezing out a barely significant victory, which is going to be a reach right now. You don’t add patients to your trial because you’re confident in the data. Either they underestimated how to do a clinical trial or overestimated their perceived benefit. Neither of which is good.
SeaStar Medical was not strictly obligated to comply with the DSMB’s recommendation to increase the NEUTRALIZE-AKI trial enrollment from 200 to 339 patients, as DSMB recommendations are typically advisory rather than binding. However, ignoring the DSMB’s guidance would be highly unusual and risky. DSMBs are independent bodies tasked with ensuring patient safety and trial integrity, and their recommendations carry significant weight with regulatory bodies like the FDA. Disregarding the advice to expand the sample size could undermine the trial’s credibility, statistical validity, and chances of regulatory approval, as the DSMB determined the increase was necessary to confirm the potential clinical benefit signal with adequate statistical power. SeaStar’s decision to follow the recommendation and take steps to accelerate enrollment reflects a strategic choice to align with best practices and enhance the trial’s likelihood of success.
The DSMB’s recommendation to continue the NEUTRALIZE-AKI trial with no device-related safety issues and a signal of potential clinical benefit suggests the study is going well. The increase in sample size to 339 patients indicates a need to strengthen statistical power to confirm this benefit, which is a common adjustment in pivotal trials. While the extended timeline may delay results, it reflects a cautious approach to ensure robust data, not a failure. The positive safety profile and early efficacy signals, consistent with pediatric QUELIMMUNE data (75% survival at 28 days), are encouraging signs of progress.
Quite the hallucination and mental gymnastics for AI. I’ll bet it’s been have fed it a lot of positive vibes on ICU and it’s trying to let you down easy.
If there was a signal of benefit, ICU wouldve left the trial at 200 patients. Because they’re expanding the trial means they’re grasping at straws and clinging onto hope that there may be some signal of benefit. Basically they’re not confident in their current data set but still believe in their product. When the alternative is to admit failure, I don’t blame them. But the odds are much higher of failure now then they were 2 weeks ago. Super risky.
So you believe that the DSMB is irrelevant in this situation? Not disagreeing with your take, just trying to understand what was the company’s decision versus was their arm twisted by this independent review board to prolong and expand the study? Thanks.
I wouldn’t say the companies arm was twisted, moreso their had was forced.
“ICU, do you want a chance at a positive outcome? Cool, you’ll have to add at least this many patients to have a chance at statistical significance.”
I wouldn’t say the review board is irrelevant. They’re ethical statisticians to say if it’s worthwhile from both a business and ethical/patient centered view point to continue the trial or not.
Asking AI what the likelihood of success for this trial is, they put it at about 30% - I’d say it’s probably roughly 10%. We’ll see.
