Joanna PooleDec 16, 2022
Alkaline phosphatase seems to have remarkable efficacy in sepsis AKI - inactivates LPS (one reason ALP increases in inflamm?) - anyone think this will become common clinically? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004577/ #AKI #ICM #MOF #nephrology #intensivecare
Effect of alkaline phosphatase on sepsis-associated acute kidney injury patients: A systematic review and meta-analysis

This systematic review and meta-analysis were performed to evaluate kidney function in patients with sepsis-associated acute kidney injury (SA-AKI) on alkaline phosphatase (AP) therapy.PubMed, Embase, and the Cochrane Central Register of Controlled Trials ...

PubMed Central (PMC)
Show threadJoanna PooleDec 16, 2022
@Charlotte_Summers do you think the results of trials so far seem too good to be true? ^^
Show threadMahesh RamananDec 16, 2022
@jopo_dr History of magic bullet trials in sepsis warns us to be very careful with these sorts of findings. Having said that, on a cursory glance, the numbers are hard to ignore completely.
Show threadJoanna PooleDec 17, 2022
@maheshramanan yes my gut says nope nope but it has seemed promising - apparently a follow on trial called Revival has been stopped for futility of 90 day primary endpoint though! Would like to see more info about that however!
Show threadJoanna PooleDec 17, 2022
@maheshramanan here - phase 3 stopped for primary endpoint futility which was mortality at 28 days - but renal parameters improved markedly. I’m wondering, probably naievely, if the component it reduces is the CkD pathophysiology?
Show threadAndrew Conway MorrisDec 17, 2022
@jopo_dr @maheshramanan the phase II trial was negative on that end point, but in a somewhat convoluted and post-hoc analysis showed an improvement in mortality that wasn’t explained by the supposed mechanism of action. The premature closure of the phase III suggests this is not going to be a goer as a treatment to me. Perhaps if they can find a diagnostic to identify a group who may benefit, but not the clinical criteria that have been used to date.
Show threadJoanna PooleDec 17, 2022
@Mozza @maheshramanan what I’m wondering, at the moment in trials in general, is what’s the 28 day mortality endpoint and what evidence is there for it? I can imagine hyper inflammatory modes of icu death are revealed in 7-10 days and then something like ESRF will take weeks to unmask if fibrosis etc. not unique to this drug but wondering about endpoints for trials in general! So hard with syndromic organ failures as not all the same!
Show threadMahesh RamananDec 17, 2022
@jopo_dr @Mozza I personally think that we should be using institution free days as a composite outcome that covers mortality, hospital stay, readmissions, and outpatient therapies like dialysis and outpatient rehab. It also has its limitations of course, and usual issues with duration of followup (30 vs 90 vs 365 etc)
Show threadAndrew Conway Morris
@maheshramanan @jopo_dr question is what one is looking for. Direct impact on short-term mortality of a specific mechanism is important, but may not modulate the longer term effects of critical illness. Depending on cost, risk and benefit will influence choices to use therapy. As an example I routinely use hydrocortisone for shock, not because it will alter mortality but because it shortens shock apparently safely and allows patients to come off organ support faster, it’s cheap and low harm.
Dec 17, 2022 at 10:45amWeb
Show threadAndrew Conway MorrisDec 17, 2022
@maheshramanan @jopo_dr not saying we shouldn’t use longer term outcomes, but we should be wary of dumping treatments because they don’t significantly alter longer term outcomes which can be influenced by multiple other factors.
Show threadMahesh RamananDec 17, 2022
@Mozza @jopo_dr Fair point. I was thinking more about landmark primary outcomes for phase 3 trials.