D5W is common, sure. My post makes no complaint about D5W being uncommon.

The problem here, again, is that this choice led to both sodium and ascorbate administration being different between the two arms. They think they are testing the ascorbate, but they can’t exclude the possibility that they are getting results due to sodium.

Since you used this as an opportunity to plug your company, I will say that the company’s claims about reducing mortality from glucose management seem very poorly supported. Your site only lists retrospective studies, but you will need multicenter prospective RCTs to have any credibility with such bombastic claims. Saying that “mortality decreases” is easily read as causal language, but there is no data supporting such language. If the effect size is anywhere near as large as you claim, these trials will be very easy to run and won’t need a large sample size.

There are several multicenter RCTs showing the efficacy of glucose control, but none as yet that do it well in a fully automated way. We don't have these studies listed on the website, and that's one thing we could definitely change, but they're pretty easy to find in the literature.

You're correct though, that the number of patients needed to demonstrate efficacy in a pivotal trial will be somewhere in the 100-300 range, which is something we're working up to! As with all things in medicine, these things take lots time and lots of capital, but the need is clear and for people who understand that need, there are very few who wouldn't want to incorporate a fully automated glucose control system into their unit.

Regarding mortality reduction claims, I'd encourage you to read the work of Van DeBerghe, Krinsley, Kovatchev, Hovorka, Chase, and Umpierrez, to name but a few of the academics who have run larger studies

Van DeBerghe is cited in the editorial discussing the pivotal practice-changing RCT that showed increased mortality from tight glucose control in the ICU (Finfer NEJM 2009). I think a lot of us intuitively believe that there is a mechanism of glucose control that should be helpful, but like I said, an RCT (of the specific device) will be necessary.

Absolutely! Yeah, NICE-SUGAR definitely has its flaws, the main one being that it has a lot more hypoglycemia than it should - a combination of the open loop protocol, infrequent sample time, no patient model, and static dosing protocol with only rescue bolusing. We did a series of simulation studies a few years ago comparing various state of the art ICU controllers, and while NICE-SUGAR has excellent time in range, it has poor performance in the hypo range, which has been linked to increased mortality.

The key is to get low variability and lots of time in range, but absolutely no hypoglycemia of any kind. That's what it's going to take to crack this problem. We hope our second human trial will continue to show those characteristics, and in a few years, an RCT pivotal trial.

Here's the NICE-SUGAR protocol for your reference: https://studies.thegeorgeinstitute.org/nice/docs/ALGORITHM.p...