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@kellumja @CCCNPitt @STARRTAKI Thank you for the opportunity to discuss @STARRTAKI today with @CCCNPitt – it was a pleasure #C3NJC
@drseanbagshaw @CCCNPitt @STARRTAKI #C3NJC. Fantastic. I want to thank trial co-chair, Professor Sean Bagshaw and congratulate the STARRT investigators for this remarkable achievement. I’m John Kellum, Director of the Center for Critical Care Nephrology and I hope you’ve enjoyed this Journal Club.
@kellumja @CCCNPitt @STARRTAKI 2/3 We aim to present secondary analyses from @STARRTAKI in the coming months to provide more context and further inform practice #C3NJC #starrtaki
@kellumja @CCCNPitt @STARRTAKI 1/3 Updates to CPGs will have to consider @STARRTAKI - no survival benefit to early (accelerated) start to RRT compared with delayed (standard) and that this strategy may come with hazards – greater RRT dependence (NNH 23) and AEs (NNH 16) #C3NJC #starrtaki
@kellumja @CCCNPitt @STARRTAKI 3/4 @STARRTAKI showed AE, which were more focused on RRT-related complications, were more common in the accelerated (23.0%) compared with standard (16.5%), due to more hypotension and hypoPO4, no difference in SAE #C3NJC #starrtaki
@kellumja @CCCNPitt @STARRTAKI 1/4 For sure @STARRTAKI showed that an accelerated-strategy contributed to greater risk of RRT dependence at 90-days (10.4% vs. 6.0%; RR 1.74; 1.24-2.43) compared with a standard-strategy #C3NJC #starrtaki
@kellumja @CCCNPitt @STARRTAKI This is shown in Fig S3 of the supplement in a competing risk analysis #C3NJC #starrtaki. This may not be totally surprising - but we are still working on further analyses to better understand these patients
@drseanbagshaw @CCCNPitt @STARRTAKI #C3NJC. I noticed that 12% of patients in the standard arm died prior to RRT. Can you talk about this finding?
@kellumja @CCCNPitt @STARRTAKI Perhaps @STARRTAKI provides robust evidence on this issue, but clinicians still face uncertainty at the bedside. This is evident by the 33.9% of patients having RRT starting without a trial-specific indication. I certainly believe there is more work to be done #C3NJC
@drseanbagshaw @CCCNPitt @STARRTAKI #C3NJC. Does this mean that some people benefit from accelerated timing but we just don’t know who? Or does it mean that starting RRT now or 25 hours from now is pretty much the same?
@drseanbagshaw @CCCNPitt @STARRTAKI #C3NJC. So, overall survival was completely the same. However, we know that in the standard group there were winners and losers—38% never received RRT and as we just said, most did OK. That means that those in standard arm who got RRT must have done worse. Correct?
@kellumja @CCCNPitt @STARRTAKI 4/4 Take home – within the context of @STARRTAKI - an accelerated-strategy did not provide a survival advantage compared to a delayed-strategy to starting RRT among critically ill patients with severe AKI #C3NJC
@kellumja @CCCNPitt @STARRTAKI 3/4 This result was also robust when assessed across worldwide geographic locations #C3NJC
@kellumja @CCCNPitt @STARRTAKI 2/4 This result was robust in pre-planned sensitivity analyses including adjusted, “as-treated”, across subgroups (sex, eGFR, sepsis, SAPS II, surgical), and across deciles of SAPS II score (no heterogeneity in treatment effect) #C3NJC
@kellumja @CCCNPitt @STARRTAKI 1/4 I was somewhat surprised! We hypothesized long-ago that earlier may be better - but we found no difference in the primary endpoint of 90-day all-cause mortality – 43.9% in accelerated and 43.7% in standard (RR 1.00, 0.93-1.09) #C3NJC #starrtaki
@drseanbagshaw @CCCNPitt @STARRTAKI #C3NJC. OK, I guess its time to discuss the primary endpoint. Were you surprised? What do you believe the take-home message is?
@kellumja @CCCNPitt @STARRTAKI In preliminary analysis, among those in the standard-strategy not starting RRT (38.2%), 32.2% died - median survival was 7.2 days (IQR, 2.1 to 26.1) and among survivors, 72.3% had kidney function return to baseline #C3NJC #starrtaki
@kellumja @CCCNPitt @STARRTAKI You didn't. We know there were 559 patients (38.2%) that did not receive RRT in the standard-strategy. We are still working on this analysis #C3NJC #starrtaki
@kellumja @CCCNPitt @STARRTAKI We are planning further analysis to better understand this; but these would be examples of patients who were started on RRT at the discretion of their treating clinicians #C3NJC #starrtaki
@drseanbagshaw @CCCNPitt @STARRTAKI #C3NJC. Sean, I found it interesting that only 597 of 903 (66.1%) of patients in the standard arm who received RRT fulfilled any of the prespecified indications for initiation. So presumably the remaining third were started despite your recommendations. Can you comment on this?
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