Lessening Organ Dysfunction With VITamin C - COVID-19 (LOVIT-COVID)
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|ClinicalTrials.gov Identifier: NCT04401150|
Recruitment Status : Not yet recruiting
First Posted : May 26, 2020
Last Update Posted : May 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Vitamin C COVID-19 Hospitalized Patients||Drug: Vitamin C Drug: Control||Phase 3|
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||800 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized controlled trial|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Only the pharmacist of the participating site will be unblinded for the preparation of the study drug to be administered.|
|Official Title:||Lessening Organ Dysfunction With VITamin C - COVID|
|Estimated Study Start Date :||June 2020|
|Estimated Primary Completion Date :||November 2021|
|Estimated Study Completion Date :||January 2022|
Experimental: Vitamin C
Vitamin C: 50 mg/kg of weight administered intravenously every 6 hours for 96 hours (16 doses).
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
Placebo Comparator: Control
Normal saline (0.9% NaCl) or dextrose 5% in water (D5W) in a volume to match the vitamin C.
Dextrose 5% in water of normal saline (0.9% NaCL) in a volume to match vitamin C.
Other Name: Placebo
- Death or persistent organ dysfunction [ Time Frame: Both assessed at 28 days ]Number of deceased participants or with persistant organ dysfunction (dependency on mechanical ventilation, new renal replacement therapy, or vasopressors).
- Number of intensive care unit-free days [ Time Frame: Assessed at 21 days ]Number of whole and part study days for which the patient is alive and not admitted to an intensive care unit
- Persistent organ dysfunction-free days in ICU [ Time Frame: Assessed at 28 days ]Number of study days in ICU without persistant organ dysfunction
- Number of patients deceased at 6 months [ Time Frame: 6 months ]Mortality at 6 months
- Health related quality of life in 6-month survivors [ Time Frame: 6 months ]
Assessed by the EQ-5D-5L EuroQol questionnaire (EQ-5D-5L). The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ-5D visual analog scale (EQ VAS). The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The patient is asked to indicate her/his health state by ticking the box next to the most appropriate statement in each of the 5 dimension. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that describes the patient's health state.
The EQ-VAS records the patient's self-rated health on a vertical visual analog scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'.
- Organ function [ Time Frame: Days 1, 2, 3, 4, 7, 10, 14, 28 ]Assessed by the Sequential Organ Failure Assessment (SOFA) score. Used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different sub-scores, one each for the respiratory (PaO2/fraction of inspired oxygen FiO2) mmHg), cardiovascular (mean arterial pressure OR administration of vasopressors required), hepatic (liver bilirubin mg/dl [µmol/L]), coagulation (platelets x 103/µl), renal (kidneys creatinine (mg/dl) [µmol/L] (or urine output)), and neurological (Glasgow coma scale). The sub-score of each system ranges from 0 (best) to +4 (worst).
- Global tissue dysoxia [ Time Frame: Days 1, 3, 7 ]Assessed by serum lactate concentration
- Rate of inflammation [ Time Frame: Days 1, 3, 7 ]Assessed by interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP).
- Rate of infection [ Time Frame: Days 1, 3, 7 ]Assessed by procalcitonin (PCT).
- Rate of endothelial injury [ Time Frame: Days 1, 3, 7 ]Assessed by thrombomodulin (TM) and angiopoietin-2 (ANG-2).
- Occurrence of stage 3 acute kidney injury [ Time Frame: Up to day 28 ]Assessed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria
- Acute hemolysis [ Time Frame: Up to day 28 ]
- 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.
o hemoglobin <75 g/L AND at least 2 of the above criteria AND requires 2 units of packed red blood cells.
- Hypoglycemia [ Time Frame: During the time participants receive the 16 doses of the investigational product and the 7 days following the last dose. ]Core lab-validated glucose level <3.8 mmol/L
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04401150
|Contact: Marie-Helene Masse||819-346-1110 ext firstname.lastname@example.org|
|Contact: Julie Menard, PhD||819-346-1110 ext email@example.com|
|Principal Investigator:||François Lamontagne, MD, FRCPC, MSc||Université de Sherbrooke and CIUSSS de l'Estrie - CHUS|
|Principal Investigator:||Neill K Adhikari, MDCM, FRCPC, MSc||Sunnybrook Health Sciences Centre, University of Toronto|