Ignite Creation Date:
2025-12-24 @ 5:17 PM
Ignite Modification Date:
2025-12-29 @ 4:15 AM
Study NCT ID:
NCT04401150
Status:
COMPLETED
Last Update Posted:
2023-04-21
First Post:
2020-05-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Lessening Organ Dysfunction With VITamin C - COVID-19
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000086382', 'term': 'COVID-19'}, {'id': 'D018352', 'term': 'Coronavirus Infections'}], 'ancestors': [{'id': 'D011024', 'term': 'Pneumonia, Viral'}, {'id': 'D011014', 'term': 'Pneumonia'}, {'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D003333', 'term': 'Coronaviridae Infections'}, {'id': 'D030341', 'term': 'Nidovirales Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001205', 'term': 'Ascorbic Acid'}], 'ancestors': [{'id': 'D013400', 'term': 'Sugar Acids'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D006880', 'term': 'Hydroxy Acids'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Only the pharmacist of the participating site will be unblinded for the preparation of the study drug to be administered.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomized controlled trial'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 392}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-08-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-04', 'completionDateStruct': {'date': '2022-12-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-04-20', 'studyFirstSubmitDate': '2020-05-21', 'studyFirstSubmitQcDate': '2020-05-21', 'lastUpdatePostDateStruct': {'date': '2023-04-21', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-05-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-07-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Death or persistent organ dysfunction', 'timeFrame': 'Both assessed at 28 days', 'description': 'Number of deceased participants or with persistant organ dysfunction (dependency on mechanical ventilation, new renal replacement therapy, or vasopressors).'}], 'secondaryOutcomes': [{'measure': 'Number of intensive care unit-free days', 'timeFrame': 'Assessed at 21 days', 'description': 'Number of whole and part study days for which the patient is alive and not admitted to an intensive care unit'}, {'measure': 'Persistent organ dysfunction-free days in ICU', 'timeFrame': 'Assessed at 28 days', 'description': 'Number of study days in ICU without persistant organ dysfunction'}, {'measure': 'Number of patients deceased at 6 months', 'timeFrame': '6 months', 'description': 'Mortality at 6 months'}, {'measure': 'Health related quality of life in 6-month survivors', 'timeFrame': '6 months', 'description': "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.\n\nThe 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'."}, {'measure': 'Organ function', 'timeFrame': 'Days 1, 2, 3, 4, 7, 10, 14, 28', 'description': "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)."}, {'measure': 'Global tissue dysoxia', 'timeFrame': 'Days 1, 3, 7', 'description': 'Assessed by serum lactate concentration'}, {'measure': 'Rate of inflammation', 'timeFrame': 'Days 1, 3, 7', 'description': 'Assessed by interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP).'}, {'measure': 'Rate of infection', 'timeFrame': 'Days 1, 3, 7', 'description': 'Assessed by procalcitonin (PCT).'}, {'measure': 'Rate of endothelial injury', 'timeFrame': 'Days 1, 3, 7', 'description': 'Assessed by thrombomodulin (TM) and angiopoietin-2 (ANG-2).'}, {'measure': 'Occurrence of stage 3 acute kidney injury', 'timeFrame': 'Up to day 28', 'description': 'Assessed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria'}, {'measure': 'Acute hemolysis', 'timeFrame': 'Up to day 28', 'description': '* clinician judgment of hemolysis, as recorded in the chart, OR\n* hemoglobin drop of at least 25 g/L within 24 hours of a dose of investigational product plus 2 of the following:\n\n * reticulocyte count \\>2 times upper limit of normal at clinical site lab;\n * haptoglobin \\<lower limit of normal at clinical site lab;\n * indirect (unconjugated) bilirubin \\>2 times upper limit of normal at clinical site lab;\n * lactate dehydrogenase (LDH) \\>2 times upper limit of normal at clinical site lab.\n\nSevere hemolysis:\n\no hemoglobin \\<75 g/L AND at least 2 of the above criteria AND requires 2 units of packed red blood cells.'}, {'measure': 'Hypoglycemia', 'timeFrame': 'During the time participants receive the 16 doses of the investigational product and the 7 days following the last dose.', 'description': 'Core lab-validated glucose level \\<3.8 mmol/L'}, {'measure': 'Vitamin C volume of distribution', 'timeFrame': '8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy).', 'description': 'Assessed by chromatography-tandem mass spectrometry'}, {'measure': 'Vitamin C clearance', 'timeFrame': '8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy).', 'description': 'Assessed by chromatography-tandem mass spectrometry'}, {'measure': 'Vitamin C plasma concentration', 'timeFrame': '8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy).', 'description': 'Assessed by chromatography-tandem mass spectrometry'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Vitamin C', 'COVID-19', 'Hospitalized patients', 'Pandemic', 'Coronavirus'], 'conditions': ['Vitamin C', 'COVID-19', 'Hospitalized Patients']}, 'referencesModule': {'references': [{'pmid': '37877585', 'type': 'DERIVED', 'citation': 'LOVIT-COVID Investigators, on behalf of the Canadian Critical Care Trials Group, and the REMAP-CAP Investigators; Adhikari NKJ, Hashmi M, Tirupakuzhi Vijayaraghavan BK, Haniffa R, Beane A, Webb SA, Angus DC, Gordon AC, Cook DJ, Guyatt GH, Berry LR, Lorenzi E, Mouncey PR, Au C, Pinto R, Menard J, Sprague S, Masse MH, Huang DT, Heyland DK, Nichol AD, McArthur CJ, de Man A, Al-Beidh F, Annane D, Anstey M, Arabi YM, Battista MC, Berry S, Bhimani Z, Bonten MJM, Bradbury CA, Brant EB, Brunkhorst FM, Burrell A, Buxton M, Cecconi M, Cheng AC, Cohen D, Cove ME, Day AG, Derde LPG, Detry MA, Estcourt LJ, Fagbodun EO, Fitzgerald M, Goossens H, Green C, Higgins AM, Hills TE, Horvat C, Ichihara N, Jayakumar D, Kanji S, Khoso MN, Lawler PR, Lewis RJ, Litton E, Marshall JC, McAuley DF, McGlothlin A, McGuinness SP, McQuilten ZK, McVerry BJ, Murthy S, Parke RL, Parker JC, Reyes LF, Rowan KM, Saito H, Salahuddin N, Santos MS, Saunders CT, Seymour CW, Shankar-Hari M, Tolppa T, Trapani T, Turgeon AF, Turner AM, Udy AA, van de Veerdonk FL, Zarychanski R, Lamontagne F. Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials. JAMA. 2023 Nov 14;330(18):1745-1759. doi: 10.1001/jama.2023.21407.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nAs 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.\n\nObjectives. 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).\n\nMethods. 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.\n\nRelevance. 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Confirmed diagnosis of COVID-19;\n* Admitted to hospital (ward or intensive care unit).\n\nExclusion Criteria:\n\n* Receiving or has received vasopressors during the current hospitalization;\n* 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;\n* Patient is expected to be discharged from the hospital in the next 24 hours;\n* More than 14 days have elapsed since the commencement of hospital admission with respiratory illness;\n* Known glucose-6-phosphate dehydrogenase (G6PD) deficiency;\n* Known sickle cell anemia\n* Pregnancy or breastfeeding;\n* Known allergy to vitamin C;\n* Known kidney stones within the past 1 year;\n* Received any intravenous vitamin C during this hospitalization unless incorporated in parenteral nutrition;\n* Expected death or withdrawal of life-sustaining treatments within 48 hours;\n* Previously enrolled in this study;\n* Previously enrolled in a trial for which co-enrolment is not allowed (co- enrolment to be determined case by case).\n\nThe 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.'}, 'identificationModule': {'nctId': 'NCT04401150', 'acronym': 'LOVIT-COVID', 'briefTitle': 'Lessening Organ Dysfunction With VITamin C - COVID-19', 'organization': {'class': 'OTHER', 'fullName': 'Université de Sherbrooke'}, 'officialTitle': 'Lessening Organ Dysfunction With VITamin C - COVID', 'orgStudyIdInfo': {'id': 'MP-31-2021-3741'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Vitamin C', 'description': 'Vitamin C: 50 mg/kg of weight administered intravenously every 6 hours for 96 hours (16 doses).', 'interventionNames': ['Drug: Vitamin C']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Control', 'description': 'Normal saline (0.9% NaCl) or dextrose 5% in water (D5W) in a volume to match the vitamin C.', 'interventionNames': ['Drug: Control']}], 'interventions': [{'name': 'Vitamin C', 'type': 'DRUG', 'otherNames': ['Ascorbic acid'], 'description': '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).', 'armGroupLabels': ['Vitamin C']}, {'name': 'Control', 'type': 'DRUG', 'otherNames': ['Placebo'], 'description': 'Dextrose 5% in water of normal saline (0.9% NaCL) in a volume to match vitamin C.', 'armGroupLabels': ['Control']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'J1H 5N4', 'city': 'Sherbrooke', 'state': 'Quebec', 'country': 'Canada', 'facility': 'Research Center of the CHUS', 'geoPoint': {'lat': 45.40008, 'lon': -71.89908}}, {'zip': 'J1H 5N4', 'city': 'Sherbrooke', 'state': 'Quebec', 'country': 'Canada', 'facility': 'Research Centre of the CHUS', 'geoPoint': {'lat': 45.40008, 'lon': -71.89908}}], 'overallOfficials': [{'name': 'François Lamontagne, MD, FRCPC, MSc', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Université de Sherbrooke and CIUSSS de l'Estrie - CHUS"}, {'name': 'Neill K Adhikari, MDCM, FRCPC, MSc', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Sunnybrook Health Sciences Centre, University of Toronto'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Université de Sherbrooke', 'class': 'OTHER'}, 'collaborators': [{'name': 'Lotte & John Hecht Memorial Foundation', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Co-Principal Investigator', 'investigatorFullName': 'François Lamontagne', 'investigatorAffiliation': 'Université de Sherbrooke'}}}}