NCT04404387

Lessening Organ Dysfunction With VITamin C in Septic ARDS

A Multicentre Concealed-Allocation Parallel-Group Blinded Randomized Controlled Trial to Ascertain the Effect of High-Dose Intravenous Vitamin C Compared to Placebo on Mortality or Persistent Organ Dysfunction at 28 Days in Septic Intensive Care Unit Patients

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 800 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of the study aims to compare the effect of high-dose intravenous vitamin C vs. placebo on a composite of death or persistent organ dysfunction - defined as continued dependency on mechanical ventilation, new renal replacement therapy, or vasopressors - assessed at 28 days on intensive care unit (ICU) patients. As secondary objectives, the study aims: * To compare the effect of high-dose intravenous vitamin C vs. placebo on: 1. 6-month mortality; 2. 6-month HRQoL; 3. organ function (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU); 4. global tissue dysoxia (at baseline); 5. oxygenation Index (FiO2 x Mean Airway Pressure/PaO2) (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU, and if still intubated); 6. occurrence of stage 3 acute kidney injury as defined by KDIGO (Kidney Disease: Improving Global Outcomes) criteria20; 7. acute hemolysis as defined by: * clinician judgment of hemolysis, as recorded in the chart, or * hemoglobin drop of at least 25 g/L within 24 hours of a dose of investigational product PLUS 2 of the following: * reticulocyte count \>2 times upper limit of normal at clinical site lab; * haptoglobin \< lower limit of normal at clinical site lab; * indirect (unconjugated) bilirubin \>2 times upper limit of normal at clinical site lab; * lactate dehydrogenase (LDH) \>2 times upper limit of normal at clinical site lab. Severe hemolysis: \- hemoglobin \< 75 g/L AND at least 2 of the above criteria AND requires 2 units of packed red blood cells; 8. hypoglycemia as defined as core lab-validated glucose levels of less than \< 3.8 mmol/L. * To assess baseline vitamin C levels in study participants (before the first dose of investigational product).

Detailed description

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.

Conditions

• Septic
• Acute Respiratory Distress Syndrome

Interventions

Type	Name	Description
DRUG	Administration of vitamin C	The intervention is intravenous vitamin C administered in bolus doses of 50 mg/kg mixed in a 50-mL solution of either dextrose 5% in water (D5W) or normal saline (0.9% NaCl), during 30 to 60 minutes or more for participants over 120 kg not to exceed 100 mg/minute, every 6 hours for 96 hours (i.e. 200 mg/kg/day and 16 doses in total). The other name of the drug: Ascorbic acid.
DRUG	Administration of placebo	Administration of placebo. Patients (in the control arm) will receive dextrose 5% in water (D5W) or normal saline (0.9% NaCl) in a volume to match the vitamin C. Placebo will be infused over 30 to 60 minutes or more for participants over 120 kg not to exceed 100 mg/minute as per the infusion instructions of vitamin C.

Timeline

• Start date: 2022-07-22
• Primary completion: 2024-07-01
• Completion: 2024-07-01
• First posted: 2020-05-27
• Last updated: 2024-01-31

Locations

1 site across 1 country: France