Lessening Organ Dysfunction With VITamin C in Septic ARDS

Treatment options for sepsis complicated by ARDS are limited to antimicrobials and supportive care (intravenous fluids, vasopressors, mechanical ventilation and renal replacement therapy). Recent preliminary evidence suggests that intravenous vitamin C may be the first therapy to mitigate the dysregulated cascade of events transforming an infection into sepsis. However, definitive practice changing evidence requires a large trial powered to detect a plausible, modest, and clinically important difference in mortality. The study LOVIT will be conducted simultaneously in Canada (country of coordination), France, the United States of America, the United Kingdom and Australia/New Zealand.The data from each country will be merged with the aim of reaching 4,000 patients globally (roughly 800 patients per country). Thus, in the context of increasing off-label use of vitamin C for sepsis and ongoing trials of vitamin C bundled with other pharmacological interventions, this study will constitute a rigorous assessment of the effect of vitamin C monotherapy on patient-important outcomes. Moreover, the French LOVIT-ARDS, part of LOVIT, will provide additional information on the specific subgroup of patients with sepsis and ARDS. This is a prospective multicentric randomized controlled trial. Web-based randomization system available 24/7. Eligible patients will be randomized in a 1:1 ratio to vitamin C or matching placebo. The study will use permuted blocks of undisclosed and variable size and stratify randomization by site. The study will enroll a total of at least 770 patients. Sites are expected to enroll at least 1or 2 patients per month. By enrolling 385 evaluable patients per arm, the study will have 80% power to detect a 10% absolute risk reduction (from 50% to 40%, which corresponds to a 20% relative risk reduction). Follow-up in the study for each patient: daily during ICU stay and telephone follow-up at 6 months.