Jayshil J, Patel, Rodney, Willoughby, Jennifer, Peterson, Thomas, Carver, James, Zelten, Adrienne, Markiewicz, Kaitlin, Spiegelhoff, Lauren A, Hipp, Bethany, Canales, Aniko, Szabo, Daren K, Heyland, Christian, Stoppe, Jacek, Zielonka, and Julie K, Freed
Elevated hydrogen sulfide (HIn adults with septic shock, is comparing high-dose IV hydroxocobalamin with placebo feasible?We conducted a phase 2 single-center, double-blind, allocation-concealed, placebo-controlled, parallel-group pilot randomized controlled trial comparing high-dose IV hydroxocobalamin with placebo in critically ill adults with septic shock. Patients meeting Sepsis 3 criteria were randomized 1:1 to receive a single 5-g dose of high-dose IV hydroxocobalamin or equivalent volume 0.9% saline solution as placebo. The primary outcome was study feasibility (enrollment rate, clinical and laboratory compliance rate, and contamination rate). Secondary outcomes included between-group differences in plasma HTwenty patients were enrolled over 19 months, establishing an enrollment rate of 1.05 patients per month. Protocol adherence rates were 100% with zero contamination. In the high-dose IV hydroxocobalamin group, compared to placebo, there was a greater reduction in vasopressor dose between randomization and postinfusion (-36% vs 4%, P .001) and randomization and 3-h postinfusion (-28% vs 10%, P = .019). In the high-dose IV hydroxocobalamin group, the plasma HThis pilot trial established favorable feasibility metrics. Consistent with the proposed mechanism of benefit, high-dose IV hydroxocobalamin compared with placebo was associated with reduced vasopressor dose and HClinicalTrials.gov; No.: NCT03783091; URL: www.gov.