Thiamine for Renal Protection in Septic Shock (TRPSS): A Randomized, Placebo-controlled, Clinical Trial.

Rationale: Kidney injury is common and associated with worse outcomes in patients with septic shock. Mitochondrial resuscitation with thiamine (vitamin B1) may attenuate septic kidney injury.

Objectives

To assess whether thiamine supplementation attenuates kidney injury in septic shock.

Methods

The TRPSS (Thiamine for Renal Protection in Septic Shock) trial was a multicenter, randomized, placebo-controlled trial of thiamine versus placebo in septic shock. The primary outcome was change in serum creatinine between enrollment and 72 hours after enrollment. Measurements and Main

Results

Eighty-eight patients were enrolled (42 patients received the intervention, and 46 received placebo). There was no significant between-groups difference in creatinine at 72 hours (mean difference, -0.57 mg/dl; 95% confidence interval, -1.18, 0.04; P = 0.07). There was no difference in receipt of kidney replacement therapy (14.3% vs. 21.7%, P = 0.34), acute kidney injury (as defined by stage 3 of the Kidney Disease: Improving Global Outcomes acute kidney injury scale; 54.7% vs. 73.9%, P = 0.07), or mortality (35.7% vs. 54.3%, P = 0.14) between the thiamine and placebo groups. Patients who received thiamine had more ICU-free days (median [interquartile range]: 22.5 [0.0-25.0] vs. 0.0 [0.0-23.0], P < 0.01). In the thiamine-deficient cohort (27.4% of patients), there was no difference in rates of kidney failure (57.1% thiamine vs. 81.5% placebo) or in-hospital mortality (28.6% vs. 68.8%) between groups.

Conclusions

In the TRPSS trial, there was no statistically significant difference in the primary outcome of change in creatinine over time. Patients who received thiamine had more ICU-free days, but there was no difference in other secondary outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT03550794).