Lessening Organ Dysfunction With VITamin C

NCT03680274 | Completed Phase 3 DMC

• 1 other identifier: MP-31-2019-2945
• Study Type: interventional
• Target: 872
• Locations: 1 country
• Sites: 1

Brief Summary

LOVIT 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 septic intensive care unit patients. Patients with COVID-19 are considered eligible for this study.

Conditions

Sepsis; Vitamin C; Intensive Care Unit; COVID-19; Pandemic; Coronavirus

Outcome Measures

Primary Outcomes (1)

• Number of deceased participants or with persistent organ dysfunction

  Defined as death or dependency on mechanical ventilation, renal replacement, or vasopressors

  Both assessed at 28 days

Secondary Outcomes (14)

• Number of participants with persistent organ dysfunction-free days in intensive care unit

  Up to day 28

• Number of participants deceased at 6 months

  6 months

• Score of health related quality of life in 6-month survivors

  6 months

• Global tissue dysoxia

  Days 1, 3, 7

• Organ function (including renal function)

  Days 1, 2, 3, 4, 7, 10, 14, 28

Study Arms (2)

Vitamin C

EXPERIMENTAL

Vitamin C: 50 mg/kg every 6 hours for 96 hours.

Drug: Vitamin C

Control

PLACEBO COMPARATOR

Dextrose 5% in water (D5W) or normal saline (0.9% NaCl) in a volume to match the vitamin C.

Other: Control

Interventions

Vitamin C DRUG

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, every 6 hours for 96 hours (i.e. 200 mg/kg/day and 16 doses in total).

Also known as: Ascorbic acid

Vitamin C

Control OTHER

Dextrose 5% in water (D5W) or normal saline (0.9% NaCl) in a volume to match the vitamin C.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Admitted to the intensive care unit with proven or suspected infection as the main diagnosis;
• Currently treated with a continuous IV infusion of vasopressors (norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine).

You may not qualify if:

• \> 24 hours of intensive care unit admission;
• Known Glucose-6-phosphate dehydrogenase (G6PD) deficiency;
• Pregnancy;
• 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 with which co-enrolment is not allowed.
• The LOVIT trial has broad eligibility criteria and includes patients with a primary diagnosis of sepsis of any cause (including sepsis caused by viral pathogens as COVID-19).

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Lotte & John Hecht Memorial Foundation: collaborator

Study Sites (1)

Research Center of the CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Related Publications (5)

• Muller MM, Pinto R, Lamontagne F, Adhikari NKJ, Del Sorbo L; Lessening Organ Dysfunction With Vitamin C (LOVIT) Investigators. Vitamin C Does Not Affect Platelet Counts in Patients With Sepsis: A Post hoc Analysis of the Lessening Organ Dysfunction With Vitamin C Randomized Trial. Crit Care Explor. 2025 Sep 5;7(9):e1310. doi: 10.1097/CCE.0000000000001310. eCollection 2025 Sep.

  PMID: 40927646 DERIVED

• Rynne J, Mosavie M, Masse MH, Menard J, Battista MC, Maslove DM, Del Sorbo L, St-Arnaud C, DAragon F, Fox-Robichaud A, Charbonney E, Adhikari NKJ, Lamontagne F, Shankar-Hari M; LOVIT Investigators, the Canadian Critical Care Trials Group. Sepsis subtypes and differential treatment response to vitamin C: biological sub-study of the LOVIT trial. Intensive Care Med. 2025 Jan;51(1):82-93. doi: 10.1007/s00134-024-07733-9. Epub 2025 Jan 7.

  PMID: 39774855 DERIVED

• Lamontagne F, Masse MH, Menard J, Sprague S, Pinto R, Heyland DK, Cook DJ, Battista MC, Day AG, Guyatt GH, Kanji S, Parke R, McGuinness SP, Tirupakuzhi Vijayaraghavan BK, Annane D, Cohen D, Arabi YM, Bolduc B, Marinoff N, Rochwerg B, Millen T, Meade MO, Hand L, Watpool I, Porteous R, Young PJ, D'Aragon F, Belley-Cote EP, Carbonneau E, Clarke F, Maslove DM, Hunt M, Chasse M, Lebrasseur M, Lauzier F, Mehta S, Quiroz-Martinez H, Rewa OG, Charbonney E, Seely AJE, Kutsogiannis DJ, LeBlanc R, Mekontso-Dessap A, Mele TS, Turgeon AF, Wood G, Kohli SS, Shahin J, Twardowski P, Adhikari NKJ; LOVIT Investigators and the Canadian Critical Care Trials Group. Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit. N Engl J Med. 2022 Jun 23;386(25):2387-2398. doi: 10.1056/NEJMoa2200644. Epub 2022 Jun 15.

  PMID: 35704292 DERIVED

• Lachance O, Goyer F, Adhikari NKJ, Masse MH, Bilodeau JF, Lamontagne F, Leclair MA. High-dose vitamin-C induced prolonged factitious hyperglycemia in a peritoneal dialysis patient: a case report. J Med Case Rep. 2021 May 21;15(1):297. doi: 10.1186/s13256-021-02869-4.

  PMID: 34020705 DERIVED

• Masse MH, Menard J, Sprague S, Battista MC, Cook DJ, Guyatt GH, Heyland DK, Kanji S, Pinto R, Day AG, Cohen D, Annane D, McGuinness S, Parke R, Carr A, Arabi Y, Vijayaraghavan BKT, D'Aragon F, Carbonneau E, Maslove D, Hunt M, Rochwerg B, Millen T, Chasse M, Lebrasseur M, Archambault P, Deblois E, Drouin C, Lellouche F, Lizotte P, Watpool I, Porteous R, Clarke F, Marinoff N, Belley-Cote E, Bolduc B, Walker S, Iazzetta J, Adhikari NKJ, Lamontagne F; Canadian Critical Care Trials Group. 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.

  PMID: 31915072 DERIVED

MeSH Terms

Conditions

Sepsis; COVID-19; Coronavirus Infections

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• François Lamontagne, MD FRCPC MSc

  Université de Sherbrooke and CIUSSS de l'Estrie - CHUS

  PRINCIPAL INVESTIGATOR

• Neill Adhikari, MDCM FRCPC MSc

  Sunnybrook Health Sciences Centre, University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor, professor and researcher

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: September 21, 2018
• Study Start: November 8, 2018
• Primary Completion: August 15, 2021
• Study Completion: January 24, 2022
• Last Updated: April 4, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data availability will commence after the publication of the primary and secondary analyses, with no anticipated end date.
• Access Criteria: Qualified researchers will need to sign a data sharing and access agreement and will need to confirm that data will only be used for the agreed upon purpose for which data access was granted. The decision to grant access will be made by the trial co-principal investigators, with involvement of the trial steering committee as needed. Proposals to access LOVIT data should be directed to the trial co-principal investigators via email: francois.lamontagne@usherbrooke.ca and neill.adhikari@utoronto.ca. Costs of preparing and providing partial datasets will be charged to requesting investigators.

Locations

CA (1)