Trial Outcomes & Findings for SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI) (NCT NCT04344184)
NCT ID: NCT04344184
Last Updated: 2024-04-04
Results Overview
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).
COMPLETED
PHASE2
47 participants
Over 27 days from baseline, day 60 and day 90 day
2024-04-04
Participant Flow
Participant milestones
| Measure |
Infusion
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
25
|
|
Overall Study
COMPLETED
|
22
|
25
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)
Baseline characteristics by cohort
| Measure |
Infusion
n=22 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.5 years
STANDARD_DEVIATION 13.4 • n=99 Participants
|
60.8 years
STANDARD_DEVIATION 16.6 • n=107 Participants
|
60.7 years
STANDARD_DEVIATION 15.0 • n=206 Participants
|
|
Sex/Gender, Customized
female
|
12 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Sex/Gender, Customized
male
|
10 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
|
Sex/Gender, Customized
unknown
|
0 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
21 Participants
n=99 Participants
|
24 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 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
|
11 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
25 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
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Weight at Admission (kg)
|
106 Kilograms
STANDARD_DEVIATION 29.5 • n=99 Participants
|
95.3 Kilograms
STANDARD_DEVIATION 30.2 • n=107 Participants
|
100 Kilograms
STANDARD_DEVIATION 30.0 • n=206 Participants
|
PRIMARY outcome
Timeframe: Over 27 days from baseline, day 60 and day 90 dayPopulation: All data points were not available for all subjects at follow-up, Day 27, 60, 90, due to participants not actively being admitted within the ICU and available for assessments.
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).
Outcome measures
| Measure |
Infusion
n=22 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Change in COVID Disease Status
Baseline (day 0)
|
5.09 score on a scale
Standard Deviation 0.811
|
5.48 score on a scale
Standard Deviation 0.714
|
|
Change in COVID Disease Status
Day 27
|
3.05 score on a scale
Standard Deviation 0.218
|
3.00 score on a scale
Standard Deviation 0
|
|
Change in COVID Disease Status
Day 60
|
3.00 score on a scale
Standard Deviation 0
|
2.88 score on a scale
Standard Deviation 0.600
|
|
Change in COVID Disease Status
Day 90
|
3.00 score on a scale
Standard Deviation 0
|
2.81 score on a scale
Standard Deviation 0.544
|
SECONDARY outcome
Timeframe: On days 5,7 and 14Population: Due to staffing/operational challenges in conjunction with only following participants during the ICU admission not all subjects participated in day 5, 7, \& 14 oxalate collection. During COVID, methods to limit access to potential exposure \& limited PPE restricted collection timepoints. Also, an internal facility error in collection process was noted by outside lab during processing samples. Facility process updated to include new methods, however multiple samples were unable to be processed.
Change in serum oxalate levels
Outcome measures
| Measure |
Infusion
n=12 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=21 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Renal Safety Biomarkers - Serum Oxalate
Day 5
|
8.96 umol per liter
Standard Deviation 9.41
|
10.5 umol per liter
Standard Deviation 13.0
|
|
Renal Safety Biomarkers - Serum Oxalate
Day 7
|
—
|
13.4 umol per liter
Standard Deviation 9.48
|
|
Renal Safety Biomarkers - Serum Oxalate
Day 14
|
—
|
19.0 umol per liter
Standard Deviation 0
|
SECONDARY outcome
Timeframe: On days 5,7 and 14Population: Due to staffing/operational challenges in conjunction with only following participants during the ICU admission not all subjects participated in day 5, 7, \& 14 oxalate collection. During COVID, methods to limit access to potential exposure \& limited PPE restricted collection timepoints. Also, an internal facility error in collection process was noted by outside lab during processing samples. Facility process updated to include new methods, however multiple samples were unable to be processed.
Microscopic analysis of urine for presence of oxalate stones
Outcome measures
| Measure |
Infusion
n=12 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=22 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Renal Safety Biomarkers - Urine Oxalate Stones
Day 5
|
1 Participants
|
0 Participants
|
|
Renal Safety Biomarkers - Urine Oxalate Stones
Day 7
|
0 Participants
|
0 Participants
|
|
Renal Safety Biomarkers - Urine Oxalate Stones
Day 14
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: On days 5,7 and 14Population: Due to staffing/operational challenges in conjunction with only following participants during the ICU admission not all subjects participated in day 5, 7, \& 14 oxalate collection. During COVID, methods to limit access to potential exposure \& limited PPE restricted collection timepoints. Also, an internal facility error in collection process was noted by outside lab during processing samples. Facility process updated to include new methods, however multiple samples were unable to be processed.
Renal safety will be Measured via renal safety biomarkers - 24- hour urine oxalate level
Outcome measures
| Measure |
Infusion
n=6 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=7 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Renal Safety Biomarkers - 24-hour Urine Oxalate Levels
Day 5
|
40.8 umol/day
Standard Deviation 27.0
|
21.5 umol/day
Standard Deviation 16.3
|
|
Renal Safety Biomarkers - 24-hour Urine Oxalate Levels
Day 7
|
—
|
25.5 umol/day
Standard Deviation 6.36
|
|
Renal Safety Biomarkers - 24-hour Urine Oxalate Levels
Day 14
|
92 umol/day
|
32.7 umol/day
Standard Deviation 26.7
|
SECONDARY outcome
Timeframe: Over 27 days from baselineRenal-failure free days, with AKI defined by the KDIGO criteria
Outcome measures
| Measure |
Infusion
n=22 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Acute Kidney Injury-free Days
|
7.36 Days
Standard Deviation 8.17
|
8.04 Days
Standard Deviation 8.18
|
SECONDARY outcome
Timeframe: Over 27 days from baseline, day 60 and day 90 dayMortality 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.
Outcome measures
| Measure |
Infusion
n=22 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Number of Deaths
Baseline to Day 27
|
5 Participants
|
7 Participants
|
|
Number of Deaths
Day 28 to Day 60
|
0 Participants
|
0 Participants
|
|
Number of Deaths
Day 61 to Day 90
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 0 (baseline), day 1, day 7Population: The data is not available for all subjects for all days as reflected in the numbers analyzed.
Difference in plasma ferritin levels in ng/mL, compared to baseline levels
Outcome measures
| Measure |
Infusion
n=22 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Change in Plasma Ferritin Levels
Day 0
|
917 ng/mL
Standard Deviation 1350
|
1510 ng/mL
Standard Deviation 1500
|
|
Change in Plasma Ferritin Levels
Day 1
|
694 ng/mL
Standard Deviation 845
|
1100 ng/mL
Standard Deviation 997
|
|
Change in Plasma Ferritin Levels
Day 7
|
638 ng/mL
Standard Deviation 488
|
1320 ng/mL
Standard Deviation 733
|
SECONDARY outcome
Timeframe: Day 0 (baseline), days 1, 2, 3, 4, 5, 6, and 7Population: Data was not available for all of the subjects for all of the days and therefore was not analyzed as reflected in the numbers.
Difference in D-dimer levels in mcg/mL, compared to baseline levels
Outcome measures
| Measure |
Infusion
n=22 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Change in Plasma D-dimer Levels
Baseline
|
2.85 mg/L FEU
Standard Deviation 3.45
|
5.60 mg/L FEU
Standard Deviation 6.55
|
|
Change in Plasma D-dimer Levels
Day 1
|
2.65 mg/L FEU
Standard Deviation 2.24
|
5.52 mg/L FEU
Standard Deviation 5.87
|
|
Change in Plasma D-dimer Levels
Day 2
|
2.60 mg/L FEU
Standard Deviation 2.42
|
6.32 mg/L FEU
Standard Deviation 7.04
|
|
Change in Plasma D-dimer Levels
Day 3
|
2.29 mg/L FEU
Standard Deviation 2.18
|
4.99 mg/L FEU
Standard Deviation 5.34
|
|
Change in Plasma D-dimer Levels
Day 4
|
2.71 mg/L FEU
Standard Deviation 2.57
|
3.44 mg/L FEU
Standard Deviation 3.47
|
|
Change in Plasma D-dimer Levels
Day 5
|
2.84 mg/L FEU
Standard Deviation 2.84
|
3.56 mg/L FEU
Standard Deviation 3.49
|
|
Change in Plasma D-dimer Levels
Day 6
|
2.84 mg/L FEU
Standard Deviation 373
|
4.56 mg/L FEU
Standard Deviation 5.18
|
|
Change in Plasma D-dimer Levels
Day 7
|
5.12 mg/L FEU
Standard Deviation 5.26
|
3.80 mg/L FEU
Standard Deviation 4.54
|
SECONDARY outcome
Timeframe: Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7Population: Not all of the data was available for all of the subjects as listed below for analysis.
Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels
Outcome measures
| Measure |
Infusion
n=22 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Change in Serum Lactate Dehydrogenase (LDH) Levels
Baseline
|
475 mmol/L
Standard Deviation 222
|
667 mmol/L
Standard Deviation 192
|
|
Change in Serum Lactate Dehydrogenase (LDH) Levels
Day 1
|
421 mmol/L
Standard Deviation 160
|
639 mmol/L
Standard Deviation 190
|
|
Change in Serum Lactate Dehydrogenase (LDH) Levels
Day 2
|
445 mmol/L
Standard Deviation 174
|
644 mmol/L
Standard Deviation 227
|
|
Change in Serum Lactate Dehydrogenase (LDH) Levels
Day 3
|
428 mmol/L
Standard Deviation 105
|
606 mmol/L
Standard Deviation 227
|
|
Change in Serum Lactate Dehydrogenase (LDH) Levels
Day 4
|
461 mmol/L
Standard Deviation 123
|
573 mmol/L
Standard Deviation 211
|
|
Change in Serum Lactate Dehydrogenase (LDH) Levels
Day 5
|
519 mmol/L
Standard Deviation 388
|
536 mmol/L
Standard Deviation 142
|
|
Change in Serum Lactate Dehydrogenase (LDH) Levels
Day 6
|
456 mmol/L
Standard Deviation 230
|
502 mmol/L
Standard Deviation 155
|
|
Change in Serum Lactate Dehydrogenase (LDH) Levels
Day 7
|
410 mmol/L
Standard Deviation 56.6
|
511 mmol/L
Standard Deviation 166
|
SECONDARY outcome
Timeframe: Day 0 (baseline), days 1, 2, 3, 4, 5, 6 and 7Population: Not all data available for all subjects as indicated below for analysis.
Difference in plasma IL-6 levels in pg/mL, compared to baseline levels
Outcome measures
| Measure |
Infusion
n=22 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 Participants
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Change in Plasma IL-6 Levels
Day 4
|
461 pg/mL
Standard Deviation 123
|
573 pg/mL
Standard Deviation 211
|
|
Change in Plasma IL-6 Levels
Day 5
|
519 pg/mL
Standard Deviation 388
|
536 pg/mL
Standard Deviation 142
|
|
Change in Plasma IL-6 Levels
Day 6
|
456 pg/mL
Standard Deviation 230
|
502 pg/mL
Standard Deviation 155
|
|
Change in Plasma IL-6 Levels
Day 7
|
410 pg/mL
Standard Deviation 56.6
|
511 pg/mL
Standard Deviation 166
|
|
Change in Plasma IL-6 Levels
Baseline
|
475 pg/mL
Standard Deviation 222
|
667 pg/mL
Standard Deviation 192
|
|
Change in Plasma IL-6 Levels
Day 1
|
421 pg/mL
Standard Deviation 160
|
639 pg/mL
Standard Deviation 190
|
|
Change in Plasma IL-6 Levels
Day 2
|
445 pg/mL
Standard Deviation 174
|
644 pg/mL
Standard Deviation 227
|
|
Change in Plasma IL-6 Levels
Day 3
|
428 pg/mL
Standard Deviation 105
|
606 pg/mL
Standard Deviation 227
|
SECONDARY outcome
Timeframe: At 28-daysPopulation: The analyzed population did not reflect all participants still in the study at this time point due to only collecting data for participants remaining in the ICU.
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
Outcome measures
| Measure |
Infusion
n=2 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Number of Patients Alive and Free of Respiratory Failure
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At 28-daysPopulation: The analyzed population did not reflect all participants still in the study at this time point due to only collecting data for participants remaining in the ICU.
Number of patients alive and not requiring invasive mechanical ventilation. The results represent the number of patients who were ventilator free.
Outcome measures
| Measure |
Infusion
n=2 Participants
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Number of Patients Alive and Free of Invasive Mechanical Ventilation
|
2 Participants
|
—
|
Adverse Events
Infusion
Placebo
Serious adverse events
| Measure |
Infusion
n=22 participants at risk
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 participants at risk
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Cardiac disorders
While on study, a subject experienced arrythmia possible ventricular tachycardia (VT) and cardiac ar
|
0.00%
0/22 • 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
|
4.0%
1/25 • Number of events 1 • 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
|
Other adverse events
| Measure |
Infusion
n=22 participants at risk
L-Ascorbic Acid (Vitamin C), intravenous infusion
L-ascorbic acid: 50 mg/kg intravenous vitamin C infusion every 6 hours for up to 96 hours
|
Placebo
n=25 participants at risk
Dextrose 5% Water
Placebo: Dextrose 5% Water
|
|---|---|---|
|
Cardiac disorders
Vtach episode during study drug infusion
|
0.00%
0/22 • 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
|
8.0%
2/25 • Number of events 2 • 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
|
|
General disorders
Infiltrated IV
|
0.00%
0/22 • 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
|
4.0%
1/25 • Number of events 1 • 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
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place