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 patient 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 Thiamine for Renal Protection in Septic Shock (TRPSS) trial was a multicenter, randomized, placebo-controlled trial of thiamine vs. placebo in septic shock. The primary outcome was change in serum creatinine between enrollment and 72 hours after enrollment. Measurement and Main Results: Eighty-eight patients were enrolled (42 patients received the intervention and 46 received placebo). There was no significant between-group difference in creatinine at 72-hours (mean difference -0.57, mg/dL, 95% CI -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), KDIGO-3 acute kidney injury (54.7% vs. 73.9%, p=0.07), or mortality (35.7% vs. 54.3%, p=0.14) between thiamine vs. placebo groups. Patients who received thiamine had more intensive care unit-free days (median 22.5 [IQR 0.0, 25.0] vs. 0.0 [IQR 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 receiving thiamine had more intensive care unit-free days, but no difference in other secondary outcomes. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT03550794.