Lessening Organ dysfunction with VITamin C (LOVIT): protocol for a randomized controlled trial

Trials. 2020 Jan 8;21(1):42. doi: 10.1186/s13063-019-3834-1.


Background: Sepsis is a health problem of global importance; treatments focus on controlling infection and supporting failing organs. Recent clinical research suggests that intravenous vitamin C may decrease mortality in sepsis. We have designed a randomized controlled trial (RCT) to ascertain the effect of vitamin C on the composite endpoint of death or persistent organ dysfunction at 28 days in patients with sepsis.

Methods: LOVIT (Lessening Organ dysfunction with VITamin C) is a multicenter, parallel-group, blinded (participants, clinicians, study personnel, Steering Committee members, data analysts), superiority RCT (minimum n = 800). Eligible patients have sepsis as the diagnosis for admission to the intensive care unit (ICU) and are receiving vasopressors. Those admitted to the ICU for more than 24 h are excluded. Eligible patients are randomized to high-dose intravenous vitamin C (50 mg/kg every 6 h for 96 h) or placebo. The primary outcome is a composite of death or persistent organ dysfunction (need for vasopressors, invasive mechanical ventilation, or new and persisting renal replacement therapy) at day 28. Secondary outcomes include persistent organ dysfunction-free days to day 28, mortality and health-related quality of life at 6 months, biomarkers of dysoxia, inflammation, infection, endothelial function, and adverse effects (hemolysis, acute kidney injury, and hypoglycemia). Six subgroup analyses are planned.

Discussion: This RCT will provide evidence of the effect of high-dose intravenous vitamin C on patient-important outcomes in patients with sepsis.

Trial registration: clinicaltrials.gov, NCT03680274, first posted 21 September 2018.

Keywords: biomarkers; randomized controlled trial; sepsis; septic shock; vitamin C.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / epidemiology
  • Administration, Intravenous
  • Adult
  • Antioxidants / administration & dosage*
  • Antioxidants / adverse effects
  • Ascorbic Acid / administration & dosage*
  • Ascorbic Acid / adverse effects
  • Clinical Trials, Phase III as Topic
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Female
  • Hemolysis / drug effects
  • Hospital Mortality
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / epidemiology
  • Intensive Care Units / statistics & numerical data
  • Male
  • Middle Aged
  • Multiple Organ Failure / epidemiology*
  • Multiple Organ Failure / etiology
  • Multiple Organ Failure / prevention & control
  • Quality of Life
  • Sepsis / complications
  • Sepsis / drug therapy*
  • Sepsis / mortality
  • Treatment Outcome
  • Vasoconstrictor Agents / administration & dosage*
  • Vasoconstrictor Agents / adverse effects


  • Antioxidants
  • Vasoconstrictor Agents
  • Ascorbic Acid

Associated data

  • ClinicalTrials.gov/NCT03680274