Trial Outcomes & Findings for Administration of Intravenous Vitamin C in Novel Coronavirus Infection (COVID-19) and Decreased Oxygenation (NCT NCT04357782)
NCT ID: NCT04357782
Last Updated: 2022-02-25
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Days 1-4
Results posted on
2022-02-25
Participant Flow
38 screened upon admission to hospital with positive severe acute respiratory syndrome (SARS)-Coronavirus (CoV)-2 infection and hypoxemia. Seven declined consent, six had history of nephrolithiasis, four had chronic kidney disease stage IV or V, one had glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Participant milestones
| Measure |
Mild Hypoxemia
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
9
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Mild Hypoxemia
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Overall Study
Discharged from hospital
|
1
|
0
|
|
Overall Study
Death
|
0
|
2
|
Baseline Characteristics
Administration of Intravenous Vitamin C in Novel Coronavirus Infection (COVID-19) and Decreased Oxygenation
Baseline characteristics by cohort
| Measure |
Mild Hypoxemia
n=10 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.5 years
n=99 Participants
|
65.0 years
n=107 Participants
|
63.5 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Admission to Intensive Care Unit (ICU)
|
2 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Hypertension
|
6 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Hyperlipidemia
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Obesity, any class
|
8 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Diabetes
|
2 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Chronic Obstructive Lung Disease (COPD)
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Immunocompromised
|
4 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Chronic Kidney Disease (CKD), any stage
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Chronic liver disease
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Congestive heart failure
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Days 1-4Occurrence 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
Outcome measures
| Measure |
Mild Hypoxemia
n=10 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Number of Participants With Adverse Events Related to High Dose Intravenous Vitamin C (HDIVC)
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Days 1-4Number of participants with serious adverse events during study drug infusion
Outcome measures
| Measure |
Mild Hypoxemia
n=10 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Number of Participants With Serious Adverse Reactions
|
0 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: Days 1-4Number of participants with adverse reactions during study drug infusion
Outcome measures
| Measure |
Mild Hypoxemia
n=10 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Number of Participants With Adverse Reactions
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Days 1-28Documented days free off mechanical ventilation the first 28 days post enrollment
Outcome measures
| Measure |
Mild Hypoxemia
n=10 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Ventilator-free Days
|
28 days
Interval 0.0 to 28.0
|
23.5 days
Interval 0.0 to 25.0
|
SECONDARY outcome
Timeframe: Days 1-28Documented days free of ICU admission the first 28 days post enrollment
Outcome measures
| Measure |
Mild Hypoxemia
n=10 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Intensive Care Unit (ICU)-Free Days
|
28 days
Interval 0.0 to 28.0
|
13.5 days
Interval 0.0 to 22.0
|
SECONDARY outcome
Timeframe: Days 1-28Documented days free of hospital admission the first 28 days post enrollment
Outcome measures
| Measure |
Mild Hypoxemia
n=10 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Hospital-free Days
|
21.5 days
Interval 21.0 to 28.0
|
8.5 days
Interval 5.0 to 24.0
|
SECONDARY outcome
Timeframe: Days 1-28Incidence of mortality at 28 days by all causes
Outcome measures
| Measure |
Mild Hypoxemia
n=10 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
All-cause Mortality
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Days 1-4oxygen 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
Outcome measures
| Measure |
Mild Hypoxemia
n=10 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Change in S/F Ratio During High Dose Intravenous Vitamin C (HDIVC)
|
108 ratio
Standard Deviation 121
|
26 ratio
Standard Deviation 140
|
SECONDARY outcome
Timeframe: Days 1-4The 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.
Outcome measures
| Measure |
Mild Hypoxemia
n=9 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=9 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
C-reactive Protein (CRP)
|
-3.8 mg/dL
Standard Deviation 5.1
|
-2.0 mg/dL
Standard Deviation 6.7
|
SECONDARY outcome
Timeframe: Days 1-4The 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.
Outcome measures
| Measure |
Mild Hypoxemia
n=9 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=8 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Lactate Dehydrogenase (LDH)
|
-42 IU/L
Standard Deviation 131
|
118 IU/L
Standard Deviation 497
|
SECONDARY outcome
Timeframe: Days 1-4The 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.
Outcome measures
| Measure |
Mild Hypoxemia
n=8 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=9 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
D-dimer
|
-0.21 ug/mL
Standard Deviation 0.72
|
3.71 ug/mL
Standard Deviation 6.9
|
SECONDARY outcome
Timeframe: Days 1-4The 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.
Outcome measures
| Measure |
Mild Hypoxemia
n=8 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=7 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Lymphocyte Count
|
329 10^3 cells/uL
Standard Deviation 514
|
276 10^3 cells/uL
Standard Deviation 581
|
SECONDARY outcome
Timeframe: Days 1-4The NLR will be calculated by dividing the absolute neutrophil count (10e3/uL) over the absolute lymphocyte count (10e3/uL) The change was determined from two time points ie Day 4 value minus Day 1 value.
Outcome measures
| Measure |
Mild Hypoxemia
n=8 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=7 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Neutrophil to Lymphocyte Ratio (NLR)
|
-0.89 ratio
Standard Deviation 4.8
|
-0.04 ratio
Standard Deviation 5.0
|
SECONDARY outcome
Timeframe: Days 1-4The difference in serum ferritin will be calculated from the start of HDIVC infusion to day 4 and reported as ng/mL The change was determined from two time points ie Day 4 value minus Day 1 value.
Outcome measures
| Measure |
Mild Hypoxemia
n=9 Participants
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=8 Participants
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Serum Ferritin
|
-299 ng/mL
Standard Deviation 449
|
-1170 ng/mL
Standard Deviation 2997
|
Adverse Events
Mild Hypoxemia
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Severe Hypoxemia
Serious events: 3 serious events
Other events: 6 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Mild Hypoxemia
n=10 participants at risk
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 participants at risk
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
20.0%
2/10 • Number of events 2 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
20.0%
2/10 • Number of events 2 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
Cardiac disorders
Pulseless Electrical Activity Arrest
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
20.0%
2/10 • Number of events 2 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
Hepatobiliary disorders
ischemic hepatitis
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
10.0%
1/10 • Number of events 1 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
Other adverse events
| Measure |
Mild Hypoxemia
n=10 participants at risk
S/F ratio \>250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
Severe Hypoxemia
n=10 participants at risk
S/F ratio ≤250 prior to Vitamin C infusion
L-ascorbic acid: 50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)
|
|---|---|---|
|
Hepatobiliary disorders
Elevated ALT
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
10.0%
1/10 • Number of events 1 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
Gastrointestinal disorders
Nausea, self-limited
|
10.0%
1/10 • Number of events 1 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
General disorders
Dry Mouth
|
20.0%
2/10 • Number of events 2 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
10.0%
1/10 • Number of events 1 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
10.0%
1/10 • Number of events 1 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
Blood and lymphatic system disorders
Bacteremia
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
20.0%
2/10 • Number of events 2 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
General disorders
Chest Pain
|
10.0%
1/10 • Number of events 1 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
20.0%
2/10 • Number of events 2 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/10 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
10.0%
1/10 • Number of events 1 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
|
Cardiac disorders
Atrial Fibrillation
|
10.0%
1/10 • Number of events 1 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
10.0%
1/10 • Number of events 1 • Data were collected systemically daily during study drug infusion and by electronic record review over the course of 28 days since study enrollment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place