LOVIT-COVID is 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 hospitalized COVID-19 patients.
Background. Research suggests that vitamin C is potentially lifesaving in the intense
inflammatory cascade such as that associated with COVID-19. Inflammation and oxidative stress
are among the main mechanisms underlying COVID-19-associated acute hypoxemic respiratory
failure. Previous evidence had also already established that a dysregulated inflammatory
cascade may distinguish patients who transition from a relatively mild viral pneumonitis to
acute respiratory distress syndrome and multiorgan failure. As such, adjunct immune
modulation therapies may improve outcomes of COVID-19 patients who are hospitalized. Numerous
preclinical studies have shown that, in addition to direct scavenging of oxygen radicals,
vitamin C limits their production and restores endothelial function.
As the majority of hospitalized patients with COVID-19 are not critically ill, avoiding
clinical deterioration and subsequent intensive care unit admission is a high priority.
Participation in research should be offered before patients become critically ill, at which
time many perceive that treatment may be too late. It is important to ensure that as many
COVID-19 patients as possible are offered the opportunity to participate to research since
that is generally the only means to access investigational therapies. The proposed trial will
address this gap, by evaluating the efficacy of intravenous vitamin C in hospitalized
patients with confirmed COVID-19.
Objectives. The overarching objective, which is identical to the objective of the parent
LOVIT trial (NCT 03680274), is to determine whether intravenous vitamin C, compared to
placebo, reduces morbidity and mortality in patients hospitalized with COVID-19. To ascertain
the volume of distribution, clearance, and plasma concentration over a course of 96 hours of
intravenous vitamin C 50 mg/kg of weight every 6 hours or matching placebo (pharmacokinetic
(PK) substudy).
Methods. Patients will be randomly assigned to vitamin C (intravenous, 50 mg/kg every 6h) or
placebo (0.9% NaCl or dextrose 5% in water) for 96 hours. Study personnel at the clinical
sites will document the composite of death or persistent organ dysfunction at day 28. Daily
assessments will occur for organ function, on days 1, 3, 7 for inflammation, infection, and
endothelial injury biomarkers, at baseline for vitamin C level, and at 6 months for mortality
and HRQoL. The LOVIT-COVID Trial will be conducted in Canadian and possibly international
sites. For the PK substudy: Blood samples will be drawn around the 8th dose at time 0 and
then after administration at times 1h, 2h, 4h and 6h (the 6h level will be immediately prior
to the next dose). The PK substudy will be conducted with 100 participants in some of the
participating centers.
Relevance. A growing body of evidence suggests that vitamin C, an inexpensive and readily
available intervention, is potentially lifesaving in sepsis and may also be beneficial in
COVID-19. LOVIT-COVID will constitute rigorous assessments of the effect of vitamin C
monotherapy on patient-important outcomes. If proven effective, vitamin C could be used
worldwide and drastically change outcomes in high- and low-income settings alike.
Drug: Vitamin C
Intravenous vitamin C administered in bolus doses of 50 mg/kg mixed in a 50-ml solution of either normal saline (0.9% NaCl) or dextrose 5% in water (D5W) during 30 to 60 minutes, every 6 hours for 96 hours (i.e. 200 mg/kg/day and 16 doses in total).
Other Name: Ascorbic acid
Drug: Control
Dextrose 5% in water of normal saline (0.9% NaCL) in a volume to match vitamin C.
Other Name: Placebo
Inclusion Criteria:
- Confirmed diagnosis of COVID-19;
- Admitted to hospital (ward or intensive care unit).
Exclusion Criteria:
- Receiving or has received vasopressors during the current hospitalization;
- More than 24 hours has elapsed since receipt of non-invasive ventilatory support
(high-flow nasal cannula or continuous positive airway pressure or non-invasive
ventilation) or invasive mechanical ventilation;
- Patient is expected to be discharged from the hospital in the next 24 hours;
- More than 14 days have elapsed since the commencement of hospital admission with
respiratory illness;
- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency;
- Known sickle cell anemia
- Pregnancy or breastfeeding;
- Known allergy to vitamin C;
- Known kidney stones within the past 1 year;
- Received any intravenous vitamin C during this hospitalization unless incorporated in
parenteral nutrition;
- Expected death or withdrawal of life-sustaining treatments within 48 hours;
- Previously enrolled in this study;
- Previously enrolled in a trial for which co-enrolment is not allowed (co- enrolment to
be determined case by case).
The trial has broad eligibility criteria and includes all COVID-19 patients admitted to the
hospital (e.g. hospital ward or the intensive care unit) who are not receiving
vasopressors.
Research Center of the CHUS
Sherbrooke, Quebec, Canada
Research Centre of the CHUS
Sherbrooke, Quebec, Canada