Vitamin C and Septic Shock

• ClinicalTrials.gov Identifier: NCT03338569
• Recruitment Status: Completed
• First Posted: November 9, 2017
• Results First Posted: July 14, 2021
• Last Update Posted: July 14, 2021
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Septic Shock; Sepsis
• Interventions: Drug: Vitamin C; Drug: Placebo
• Enrollment: 125

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Placebo	Intervention
Arm/Group Description	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Period Title: Overall Study
Started	64	61
Completed	56	56
Not Completed	8	5
Reason Not Completed
Physician Decision	8	3
Withdrawal by Subject	0	1
Lost to Follow-up	0	1

Baseline Characteristics

Arm/Group Title		Placebo	Intervention	Total
Arm/Group Description		Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C	Total of all reporting groups
Overall Number of Baseline Participants		64	61	125
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	64 participants	61 participants	125 participants
		73; (60.7 to 80)	68.9; (60.1 to 79.9)	71; (60.1 to 80)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	64 participants	61 participants	125 participants
	Female	31 48.4%	31 50.8%	62 49.6%
	Male	33 51.6%	30 49.2%	63 50.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	64 participants	61 participants	125 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	2 3.1%	2 3.3%	4 3.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 3.1%	0 0.0%	2 1.6%
	White	59 92.2%	59 96.7%	118 94.4%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 1.6%	0 0.0%	1 0.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	64 participants	61 participants	125 participants
		64	61	125

Outcome Measures

1. Primary Outcome

Title	Number of Participants With ICU Mortality
Description	Outcome is reported as the number of patients who expired while receiving care in the intensive care unit (ICU).
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	64	61
Measure Type: Count of Participants; Unit of Measure: Participants
	20 31.3%	14 23.0%

2. Primary Outcome

Title	All Cause Mortality at 28 Days
Description	Outcome is reported as the number of participants who have expired at 28 days post intervention
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	64	61
Measure Type: Count of Participants; Unit of Measure: Participants
	26 40.6%	16 26.2%

3. Secondary Outcome

Title	Duration of Vasopressor Therapy
Description	Outcome is reported as the duration in hours of vasopressor therapy post intervention administration
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	64	61
Median (Inter-Quartile Range); Unit of Measure: hours
	27.1; (16.4 to 45.2)	27.7; (13.6 to 47.6)

4. Secondary Outcome

Title	Duration of ICU Stay Post Intervention Administration
Description	Outcome is reported as the duration (in days) that participants require care in the intensive care unit (ICU) post intervention administration
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	64	61
Mean (Inter-Quartile Range); Unit of Measure: days
	2.6; (1.5 to 5.3)	2.9; (1.8 to 7.5)

5. Secondary Outcome

Title	Time to Lactate Clearance Post Intervention Administration
Description	[Not Specified]
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Measure was not collected

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

6. Secondary Outcome

Title	Rate of Lactate Clearance Post Intervention Administration
Description	Outcome is reported as the number of participants who clear lactate from the bloodstream at 24, 48, 72, and 96 hours post intervention. Clearance is defined as a serum concentration of 2.0 mmol/l or less.
Time Frame	24, 48, 72, and 96 hours post intervention

Outcome Measure Data

Analysis Population Description

All participants who completed 96 hours of testing are included.

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	45	43
Measure Type: Count of Participants; Unit of Measure: Participants
24 hours	13 28.9%	12 27.9%
48 hours	18 40.0%	16 37.2%
72 hours	18 40.0%	18 41.9%
96 hours	19 42.2%	18 41.9%

7. Secondary Outcome

Title	Rate of Procalcitonin Clearance Post Intervention Administration
Description	[Not Specified]
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Outcome was not collected.

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

8. Secondary Outcome

Title	Number of Participants With Need for Renal Replacement Therapy
Description	Outcome is reported as the number of participants who require renal replacement therapy
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	64	61
Measure Type: Count of Participants; Unit of Measure: Participants
	2 3.1%	10 16.4%

9. Secondary Outcome

Title	Change in Serum Creatinine
Description	Outcome is report as the change in serum creatinine between baseline and 4 days following treatment. Outcome is reported in units of mg/dl.
Time Frame	Baseline and 4 days

Outcome Measure Data

Analysis Population Description

All participants for whom baseline and 96-hour creatinine data is available are included in this analysis.

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	56	49
Median (Inter-Quartile Range); Unit of Measure: mg/dl
	0.5; (-0.1 to 0.7)	.4; (0 to 0.7)

10. Secondary Outcome

Title	Change in Sequential Organ Failure Assessment (SOFA) Score
Description	SOFA score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems. Total scores range from 0 to 24, with higher scores indicating higher likely mortality.
Time Frame	Baseline and 4 days

Outcome Measure Data

Analysis Population Description

All participants for whom baseline and 96-hour SOFA scores were available are included in this analysis.

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	61	58
Median (Inter-Quartile Range); Unit of Measure: score on a scale
	4; (2 to 6)	4; (2 to 6)

11. Secondary Outcome

Title	Change in Acute Physiology and Chronic Health Evaluation (APACHE) Scores
Description	APACHE score is a severity-of-disease classification system that is calculated from a patient's age and 12 routine physiological measurements. Total scores are computed based on several measurements and range from 0 to 71 with higher scores corresponding to more severe disease and a higher risk of death.
Time Frame	Baseline and 4 days

Outcome Measure Data

Analysis Population Description

All participants for whom APACHE scores at baseline and 4 days post intervention were available are included.

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	61	58
Mean (Inter-Quartile Range); Unit of Measure: score on a scale
	7; (1 to 12)	5; (3 to 10)

12. Secondary Outcome

Title	Total Intravenous Fluid Administered
Description	Outcome is reported as the total volume of intravenous fluid (in liters) administered to participants during 24 hours following the initiation of study treatment.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

All participants for whom total intravenous fluid administration data was available are included.

Arm/Group Title	Placebo	Intervention
Arm/Group Description:	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Number of Participants Analyzed	64	60
Mean (Inter-Quartile Range); Unit of Measure: liters
6 hours post initiation of study treatment	.76; (.36 to 1.26)	1.07; (.72 to 1.64)
24 hours post initiation of study treatment	3.37; (1.98 to 4.7)	3.59; (2.52 to 5.02)

Adverse Events

Time Frame	28 days
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo		Intervention
Arm/Group Description	Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention		Vitamin C Vitamin C: Continuous infusion of vitamin C
All-Cause Mortality
	Placebo		Intervention
	Affected / at Risk (%)		Affected / at Risk (%)
Total	26/64 (40.63%)		16/61 (26.23%)
Serious Adverse Events
	Placebo		Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/64 (4.69%)		4/61 (6.56%)
Blood and lymphatic system disorders
Bleeding †	0/64 (0.00%)	0	1/61 (1.64%)	1
Pancytopenia †	0/64 (0.00%)	0	1/61 (1.64%)	1
Cardiac disorders
Elevated Troponin w/o ST elevation †	0/64 (0.00%)	0	2/61 (3.28%)	2
New or worsening heart failure †	2/64 (3.13%)	2	0/61 (0.00%)	0
Arrythmia †	1/64 (1.56%)	1	0/61 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo		Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/64 (14.06%)		8/61 (13.11%)
Blood and lymphatic system disorders
Thrombocytopenia †	1/64 (1.56%)	1	1/61 (1.64%)	1
Bleeding event †	1/64 (1.56%)	1	0/61 (0.00%)	0
Cardiac disorders
New or worsening heart failure †	1/64 (1.56%)	1	0/61 (0.00%)	0
Arrythmia †	3/64 (4.69%)	3	4/61 (6.56%)	7
Elevated Troponin w/o ST elevation †	1/64 (1.56%)	1	0/61 (0.00%)	0
Gastrointestinal disorders
Loose stools †	1/64 (1.56%)	1	0/61 (0.00%)	0
Nausea †	0/64 (0.00%)	0	1/61 (1.64%)	1
Dysphagia †	0/64 (0.00%)	0	1/61 (1.64%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion †	1/64 (1.56%)	1	0/61 (0.00%)	0
Skin and subcutaneous tissue disorders
Maculopapular rash †	0/64 (0.00%)	0	1/61 (1.64%)	1
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Ronald Reilkoff, MD
• Organization: University of Minnesota
• Phone: 612-624-0999
• EMail: rreilkof@umn.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wacker DA, Burton SL, Berger JP, Hegg AJ, Heisdorffer J, Wang Q, Medcraft EJ, Reilkoff RA. Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy. Crit Care Med. 2022 May 1;50(5):e458-e467. doi: 10.1097/CCM.0000000000005427. Epub 2022 Jan 5.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT03338569
• Other Study ID Numbers: STUDY00000625
• First Submitted: October 31, 2017
• First Posted: November 9, 2017
• Results First Submitted: June 14, 2021
• Results First Posted: July 14, 2021
• Last Update Posted: July 14, 2021