NCT04357782: AVoCaDO

Administration of Intravenous Vitamin C in Novel Coronavirus Infection (COVID-19) and Decreased Oxygenation

Completed Phase 1, PHASE2 Results posted Last updated 25 February 2022

What this trial tests

Phase 1, PHASE2 trial testing L-ascorbic acid in COVID-19 in 20 participants. Completed in 13 October 2020.

Timeline

16 April 2020

Primary endpoint
13 October 2020

13 October 2020

Quick facts

Lead sponsor	Hunter Holmes Mcguire Veteran Affairs Medical Center
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	20
Start date	16 April 2020
Primary completion	13 October 2020
Estimated completion	13 October 2020
Sites	1 location across United States

Drugs / interventions tested

• L-ascorbic acid — full drug profile →

Conditions studied

• COVID-19 — all drugs for COVID-19 →
• Hypoxia — all drugs for Hypoxia →

Sponsor

Hunter Holmes Mcguire Veteran Affairs Medical Center

Who can join

Adults 18 to 99, any sex, with COVID-19 or Hypoxia. 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.

Number of Participants With Adverse Events Related to High Dose Intravenous Vitamin C (HDIVC) Primary · Days 1-4

Occurrence of adverse events during study drug infusion as defined in the Ascor package insert ie acute kidney injury (increase in serum creatinine 3x baseline prior to initial HDIVC dose, hemolysis, iatrogenic hypoglycemia, pain at swelling site of infusion, crystalluria on urinalysis (UA) after last HDIVC dose

Group	Value	95% CI
Mild Hypoxemia	0
Severe Hypoxemia	0

Number of Participants With Serious Adverse Reactions Primary · Days 1-4

Number of participants with serious adverse events during study drug infusion

Group	Value	95% CI
Mild Hypoxemia	0
Severe Hypoxemia	2

Number of Participants With Adverse Reactions Primary · Days 1-4

Number of participants with adverse reactions during study drug infusion

Group	Value	95% CI
Mild Hypoxemia	1
Severe Hypoxemia	2

Ventilator-free Days Secondary · Days 1-28

Documented days free off mechanical ventilation the first 28 days post enrollment

Group	Value	95% CI
Mild Hypoxemia	28	0 – 28
Severe Hypoxemia	23.5	0 – 25

Intensive Care Unit (ICU)-Free Days Secondary · Days 1-28

Documented days free of ICU admission the first 28 days post enrollment

Group	Value	95% CI
Mild Hypoxemia	28	0 – 28
Severe Hypoxemia	13.5	0 – 22

Hospital-free Days Secondary · Days 1-28

Documented days free of hospital admission the first 28 days post enrollment

Group	Value	95% CI
Mild Hypoxemia	21.5	21 – 28
Severe Hypoxemia	8.5	5 – 24

All-cause Mortality Secondary · Days 1-28

Incidence of mortality at 28 days by all causes

Group	Value	95% CI
Mild Hypoxemia	0
Severe Hypoxemia	3

Change in S/F Ratio During High Dose Intravenous Vitamin C (HDIVC) Secondary · Days 1-4

oxygen saturation by pulse oximetry (SpO2) will be divided by fraction of inspired oxygen (FiO2) at start of study infusion and compared with S/F ratio at end of study infusion

Group	Value	95% CI
Mild Hypoxemia	108	± 121
Severe Hypoxemia	26	± 140

C-reactive Protein (CRP) Secondary · Days 1-4

The difference in serum CRP during HDIVC infusion reported in mg/dL Local lab with upper measurement limit of 19 mg/dL The change was determined from two time points ie Day 4value minus Day 1 value.

Group	Value	95% CI
Mild Hypoxemia	-3.8	± 5.1
Severe Hypoxemia	-2.0	± 6.7

Lactate Dehydrogenase (LDH) Secondary · Days 1-4

The difference in LDH during HDIVC infusion will be reported in IU/L The change was determined from two time points ie Day 4 value minus Day 1 value.

Group	Value	95% CI
Mild Hypoxemia	-42	± 131
Severe Hypoxemia	118	± 497

D-dimer Secondary · Days 1-4

The difference in D-dimer during HDIVC infusion will be reported in ug/mL The change was determined from two time points ie Day 4 value minus Day 1 value.

Group	Value	95% CI
Mild Hypoxemia	-0.21	± 0.72
Severe Hypoxemia	3.71	± 6.9

Lymphocyte Count Secondary · Days 1-4

The difference in lymphocyte count during HDIVC infusion will be reported in 10\^3 cells/uL The change was determined from two time points ie Day 4 value minus Day 1 value.

Group	Value	95% CI
Mild Hypoxemia	329	± 514
Severe Hypoxemia	276	± 581

Adverse events — posted to ClinicalTrials.gov

Time frame: Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Mild Hypoxemia

Serious: 0/10 (0%)

Deaths: 0/10

Severe Hypoxemia

Serious: 3/10 (30%)

Deaths: 3/10

Serious adverse events (4 terms)

Reaction	System	Mild Hypoxemia	Severe Hypoxemia
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Pulseless Electrical Activity Arrest	Cardiac disorders	—	—
ischemic hepatitis	Hepatobiliary disorders	—	—

Other adverse events (10 terms — click to expand)

Reaction	System	Mild Hypoxemia	Severe Hypoxemia
Dry Mouth	General disorders	—	—
Bacteremia	Blood and lymphatic system disorders	—	—
Chest Pain	General disorders	—	—
Elevated ALT	Hepatobiliary disorders	—	—
Nausea, self-limited	Gastrointestinal disorders	—	—
Thromboembolic event	Vascular disorders	—	—
Pneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Elevated ALT	Hepatobiliary disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Atrial Fibrillation	Cardiac disorders	—	—

Most-reported serious reactions: Acute respiratory failure, Acute kidney injury, Pulseless Electrical Activity Arrest, ischemic hepatitis.

Data from ClinicalTrials.gov NCT04357782 adverse events section.

Sponsor's own description

Previous research has shown that high dose intravenous vitamin C (HDIVC) may benefit patients with sepsis, acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS). However, it is not known if early administration of HDIVC could prevent progression to ARDS.

We hypothesize that HDIVC is safe and tolerable in Coronavirus disease 2019 (COVID-19) subjects given early or late in the disease course and may reduce the risk of respiratory failure requiring mechanical ventilation and development of ARDS along with reductions in supplemental oxygen demand and inflammatory markers.

Publications & conference data

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

1. The COVID-19 pandemic and physical activity.
   Woods JA, Hutchinson NT, Powers SK, Roberts WO, et al · · 2020 · cited 287× · PMID 34189484 · DOI 10.1016/j.smhs.2020.05.006
2. COVID-19: Characteristics and Therapeutics.
   Chilamakuri R, Agarwal S. · · 2021 · cited 192× · PMID 33494237 · DOI 10.3390/cells10020206
3. 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
4. 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
5. Role of vitamins and minerals as immunity boosters in COVID-19.
   Kumar P, Kumar M, Bedi O, Gupta M, et al · · 2021 · cited 75× · PMID 34110533 · DOI 10.1007/s10787-021-00826-7
6. Myth Busters: Dietary Supplements and COVID-19.
   Adams KK, Baker WL, Sobieraj DM. · · 2020 · cited 74× · PMID 32396382 · DOI 10.1177/1060028020928052
7. Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics.
   Pokharel MD, Garcia-Flores A, Marciano D, Franco MC, et al · · 2024 · cited 73× · PMID 38295575 · DOI 10.1016/j.redox.2024.103049
8. Potential Therapeutic Options for COVID-19: Current Status, Challenges, and Future Perspectives.
   Sarkar C, Mondal M, Torequl Islam M, Martorell M, et al · · 2020 · cited 64× · PMID 33041814 · DOI 10.3389/fphar.2020.572870