Last reviewed · How we verify

NCT04344184

SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)

Completed Phase 2 Results posted Last updated 4 April 2024
What this trial tests

Phase 2 trial testing L-ascorbic acid in COVID-19 in 47 participants. Completed in 10 June 2022.

Timeline
18 December 2020
Primary endpoint
10 June 2022
10 June 2022

Quick facts

Lead sponsorVirginia Commonwealth University
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment47
Start date18 December 2020
Primary completion10 June 2022
Estimated completion10 June 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Virginia Commonwealth University

Who can join

18 and older, any sex, with COVID-19 or Lung Injury, Acute. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in COVID Disease Status Primary · Over 27 days from baseline, day 60 and day 90 day

COVID disease status was measured for improvement using the World Health Organization (WHO) ordinal scale for clinical improvement of COVID-19 over ICU admission within 27 days. The WHO scale is a 9-point ordinal scale ranging from uninfected (0), ambulatory (1-2), hospitalized with severe disease (5), hospitalized with intubation and organ support (6-7) and death (score of 8).

Baseline (day 0)
GroupValue95% CI
Infusion5.09± 0.811
Placebo5.48± 0.714
Day 27
GroupValue95% CI
Infusion3.05± 0.218
Placebo3.00± 0
Day 60
GroupValue95% CI
Infusion3.00± 0
Placebo2.88± 0.600
Day 90
GroupValue95% CI
Infusion3.00± 0
Placebo2.81± 0.544
Renal Safety Biomarkers - Serum Oxalate Secondary · On days 5,7 and 14

Change in serum oxalate levels

Day 5
GroupValue95% CI
Infusion8.96± 9.41
Placebo10.5± 13.0
Day 7
GroupValue95% CI
Placebo13.4± 9.48
Day 14
GroupValue95% CI
Placebo19.0± 0
Renal Safety Biomarkers - Urine Oxalate Stones Secondary · On days 5,7 and 14

Microscopic analysis of urine for presence of oxalate stones

Day 5
GroupValue95% CI
Infusion1
Placebo0
Day 7
GroupValue95% CI
Infusion0
Placebo0
Day 14
GroupValue95% CI
Infusion0
Placebo0
Renal Safety Biomarkers - 24-hour Urine Oxalate Levels Secondary · On days 5,7 and 14

Renal safety will be Measured via renal safety biomarkers - 24- hour urine oxalate level

Day 5
GroupValue95% CI
Infusion40.8± 27.0
Placebo21.5± 16.3
Day 7
GroupValue95% CI
Placebo25.5± 6.36
Day 14
GroupValue95% CI
Infusion92
Placebo32.7± 26.7
Acute Kidney Injury-free Days Secondary · Over 27 days from baseline

Renal-failure free days, with AKI defined by the KDIGO criteria

GroupValue95% CI
Infusion7.36± 8.17
Placebo8.04± 8.18
Number of Deaths Secondary · Over 27 days from baseline, day 60 and day 90 day

Mortality by all cause was comprehensively collected using hospital encounter information over 27 days from baseline, in addition to public record review at day 60 and day 90. Results for this outcome represents the number of deaths that have occurred between each time point.

Baseline to Day 27
GroupValue95% CI
Infusion5
Placebo7
Day 28 to Day 60
GroupValue95% CI
Infusion0
Placebo0
Day 61 to Day 90
GroupValue95% CI
Infusion0
Placebo0
Change in Plasma Ferritin Levels Secondary · Day 0 (baseline), day 1, day 7

Difference in plasma ferritin levels in ng/mL, compared to baseline levels

Day 0
GroupValue95% CI
Infusion917± 1350
Placebo1510± 1500
Day 1
GroupValue95% CI
Infusion694± 845
Placebo1100± 997
Day 7
GroupValue95% CI
Infusion638± 488
Placebo1320± 733
Change in Plasma D-dimer Levels Secondary · Day 0 (baseline), days 1, 2, 3, 4, 5, 6, and 7

Difference in D-dimer levels in mcg/mL, compared to baseline levels

Baseline
GroupValue95% CI
Infusion2.85± 3.45
Placebo5.60± 6.55
Day 1
GroupValue95% CI
Infusion2.65± 2.24
Placebo5.52± 5.87
Day 2
GroupValue95% CI
Infusion2.60± 2.42
Placebo6.32± 7.04
Day 3
GroupValue95% CI
Infusion2.29± 2.18
Placebo4.99± 5.34
Day 4
GroupValue95% CI
Infusion2.71± 2.57
Placebo3.44± 3.47
Day 5
GroupValue95% CI
Infusion2.84± 2.84
Placebo3.56± 3.49
Day 6
GroupValue95% CI
Infusion2.84± 373
Placebo4.56± 5.18
Day 7
GroupValue95% CI
Infusion5.12± 5.26
Placebo3.80± 4.54
Change in Serum Lactate Dehydrogenase (LDH) Levels Secondary · Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7

Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels

Baseline
GroupValue95% CI
Infusion475± 222
Placebo667± 192
Day 1
GroupValue95% CI
Infusion421± 160
Placebo639± 190
Day 2
GroupValue95% CI
Infusion445± 174
Placebo644± 227
Day 3
GroupValue95% CI
Infusion428± 105
Placebo606± 227
Day 4
GroupValue95% CI
Infusion461± 123
Placebo573± 211
Day 5
GroupValue95% CI
Infusion519± 388
Placebo536± 142
Day 6
GroupValue95% CI
Infusion456± 230
Placebo502± 155
Day 7
GroupValue95% CI
Infusion410± 56.6
Placebo511± 166
Change in Plasma IL-6 Levels Secondary · Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7

Difference in plasma IL-6 levels in pg/mL, compared to baseline levels

Baseline
GroupValue95% CI
Infusion475± 222
Placebo667± 192
Day 1
GroupValue95% CI
Infusion421± 160
Placebo639± 190
Day 2
GroupValue95% CI
Infusion445± 174
Placebo644± 227
Day 3
GroupValue95% CI
Infusion428± 105
Placebo606± 227
Day 4
GroupValue95% CI
Infusion461± 123
Placebo573± 211
Day 5
GroupValue95% CI
Infusion519± 388
Placebo536± 142
Day 6
GroupValue95% CI
Infusion456± 230
Placebo502± 155
Day 7
GroupValue95% CI
Infusion410± 56.6
Placebo511± 166
Number of Patients Alive and Free of Respiratory Failure Secondary · At 28-days

Respiratory failure defined as resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20L/min with fraction of delivered oxygen ≥0.5), noninvasive positive pressure ventilation, extracorporeal membrane oxygenation

GroupValue95% CI
Infusion2
Placebo0
Number of Patients Alive and Free of Invasive Mechanical Ventilation Secondary · At 28-days

Number of patients alive and not requiring invasive mechanical ventilation. The results represent the number of patients who were ventilator free.

GroupValue95% CI
Infusion2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were monitored/assessed from baseline to the end of study procedures, or until participants withdrew from the study, up to day 90 for each enrolled participant. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Infusion
Serious: 0/22 (0%)
Deaths: 5/22
Placebo
Serious: 1/25 (4%)
Deaths: 7/25

Serious adverse events (1 terms)

ReactionSystemInfusionPlacebo
While on study, a subject experienced arrythmia possible ventricular tachycardia (VT) and cardiac arCardiac disorders——
Other adverse events (2 terms — click to expand)

ReactionSystemInfusionPlacebo
Vtach episode during study drug infusionCardiac disorders——
Infiltrated IVGeneral disorders——

Most-reported serious reactions: While on study, a subject experienced arrythmia possible ventricular tachycardia (VT) and cardiac ar.

Data from ClinicalTrials.gov NCT04344184 adverse events section.

Sponsor's own description

This study will evaluate the safety of a 96-hour intravenous vitamin C infusion protocol (50 mg/kg every 6 hours) in patients with hypoxemia and suspected COVID-19.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. COVID-19: Characteristics and Therapeutics.
    Chilamakuri R, Agarwal S. · · 2021 · cited 192× · PMID 33494237 · DOI 10.3390/cells10020206
  2. Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression.
    Schönrich G, Raftery MJ, Samstag Y. · · 2020 · cited 165× · PMID 32773102 · DOI 10.1016/j.jbior.2020.100741
  3. Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies.
    Market M, Angka L, Martel AB, Bastin D, et al · · 2020 · cited 115× · PMID 32655581 · DOI 10.3389/fimmu.2020.01512
  4. Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial.
    JamaliMoghadamSiahkali S, Zarezade B, Koolaji S, SeyedAlinaghi S, et al · · 2021 · cited 102× · PMID 33573699 · DOI 10.1186/s40001-021-00490-1
  5. Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies (Review).
    Nitulescu GM, Paunescu H, Moschos SA, Petrakis D, et al · · 2020 · cited 93× · PMID 32468014 · DOI 10.3892/ijmm.2020.4608
  6. The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19.
    Carr AC, Rowe S. · · 2020 · cited 89× · PMID 33121019 · DOI 10.3390/nu12113286
  7. Overview of the possible role of vitamin C in management of COVID-19.
    Abobaker A, Alzwi A, Alraied AHA. · · 2020 · cited 76× · PMID 33113146 · DOI 10.1007/s43440-020-00176-1
  8. Myth Busters: Dietary Supplements and COVID-19.
    Adams KK, Baker WL, Sobieraj DM. · · 2020 · cited 74× · PMID 32396382 · DOI 10.1177/1060028020928052

Verify or expand the search:

Other trials of L-ascorbic acid

Trials testing the same drug.

Other recruiting trials for COVID-19

Currently open trials in the same condition.

Other Virginia Commonwealth University trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04344184.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing