Trial Outcomes & Findings for Vitamin C and Septic Shock (NCT NCT03338569)

NCT ID: NCT03338569

Last Updated: 2021-07-14

Results Overview

Outcome is reported as the number of patients who expired while receiving care in the intensive care unit (ICU).

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 125 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2021-07-14

Participant Flow

Participant milestones

Measure	Placebo Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Study STARTED	64	61
Overall Study COMPLETED	56	56
Overall Study NOT COMPLETED	8	5

Reasons for withdrawal

Measure	Placebo Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention Vitamin C Vitamin C: Continuous infusion of vitamin C
Overall Study Physician Decision	8	3
Overall Study Withdrawal by Subject	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Vitamin C and Septic Shock

Baseline characteristics by cohort

Measure	Placebo n=64 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=61 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C	Total n=125 Participants Total of all reporting groups
Age, Continuous	73 years n=5 Participants	68.9 years n=7 Participants	71 years n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	31 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	30 Participants n=7 Participants	63 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	59 Participants n=5 Participants	59 Participants n=7 Participants	118 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	64 participants n=5 Participants	61 participants n=7 Participants	125 participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days

Outcome is reported as the number of patients who expired while receiving care in the intensive care unit (ICU).

Outcome measures

Measure	Placebo n=64 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=61 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
Number of Participants With ICU Mortality	20 Participants	14 Participants

PRIMARY outcome

Timeframe: 28 days

Outcome is reported as the number of participants who have expired at 28 days post intervention

Outcome measures

Measure	Placebo n=64 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=61 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
All Cause Mortality at 28 Days	26 Participants	16 Participants

SECONDARY outcome

Timeframe: 28 days

Outcome is reported as the duration in hours of vasopressor therapy post intervention administration

Outcome measures

Measure	Placebo n=64 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=61 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
Duration of Vasopressor Therapy	27.1 hours Interval 16.4 to 45.2	27.7 hours Interval 13.6 to 47.6

SECONDARY outcome

Timeframe: 28 days

Outcome is reported as the duration (in days) that participants require care in the intensive care unit (ICU) post intervention administration

Outcome measures

Measure	Placebo n=64 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=61 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
Duration of ICU Stay Post Intervention Administration	2.6 days Interval 1.5 to 5.3	2.9 days Interval 1.8 to 7.5

SECONDARY outcome

Timeframe: 28 days

Population: Measure was not collected

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24, 48, 72, and 96 hours post intervention

Population: All participants who completed 96 hours of testing are included.

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.

Outcome measures

Measure	Placebo n=45 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=43 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
Rate of Lactate Clearance Post Intervention Administration 72 hours	18 Participants	18 Participants
Rate of Lactate Clearance Post Intervention Administration 96 hours	19 Participants	18 Participants
Rate of Lactate Clearance Post Intervention Administration 24 hours	13 Participants	12 Participants
Rate of Lactate Clearance Post Intervention Administration 48 hours	18 Participants	16 Participants

SECONDARY outcome

Timeframe: 4 days

Population: Outcome was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 days

Outcome is reported as the number of participants who require renal replacement therapy

Outcome measures

Measure	Placebo n=64 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=61 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
Number of Participants With Need for Renal Replacement Therapy	2 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline and 4 days

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

Outcome is report as the change in serum creatinine between baseline and 4 days following treatment. Outcome is reported in units of mg/dl.

Outcome measures

Measure	Placebo n=56 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=49 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
Change in Serum Creatinine	0.5 mg/dl Interval -0.1 to 0.7	.4 mg/dl Interval 0.0 to 0.7

SECONDARY outcome

Timeframe: Baseline and 4 days

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

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.

Outcome measures

Measure	Placebo n=61 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=58 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
Change in Sequential Organ Failure Assessment (SOFA) Score	4 score on a scale Interval 2.0 to 6.0	4 score on a scale Interval 2.0 to 6.0

SECONDARY outcome

Timeframe: Baseline and 4 days

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

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.

Outcome measures

Measure	Placebo n=61 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=58 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
Change in Acute Physiology and Chronic Health Evaluation (APACHE) Scores	7 score on a scale Interval 1.0 to 12.0	5 score on a scale Interval 3.0 to 10.0

SECONDARY outcome

Timeframe: 24 hours

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

Outcome is reported as the total volume of intravenous fluid (in liters) administered to participants during 24 hours following the initiation of study treatment.

Outcome measures

Measure	Placebo n=64 Participants Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=60 Participants Vitamin C Vitamin C: Continuous infusion of vitamin C
Total Intravenous Fluid Administered 6 hours post initiation of study treatment	.76 liters Interval 0.36 to 1.26	1.07 liters Interval 0.72 to 1.64
Total Intravenous Fluid Administered 24 hours post initiation of study treatment	3.37 liters Interval 1.98 to 4.7	3.59 liters Interval 2.52 to 5.02

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 9 other events

Deaths: 26 deaths

Intervention

Serious events: 4 serious events

Other events: 8 other events

Deaths: 16 deaths

Serious adverse events

Measure	Placebo n=64 participants at risk Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=61 participants at risk Vitamin C Vitamin C: Continuous infusion of vitamin C
Cardiac disorders Elevated Troponin w/o ST elevation	0.00% 0/64 • 28 days	3.3% 2/61 • Number of events 2 • 28 days
Cardiac disorders New or worsening heart failure	3.1% 2/64 • Number of events 2 • 28 days	0.00% 0/61 • 28 days
Cardiac disorders Arrythmia	1.6% 1/64 • Number of events 1 • 28 days	0.00% 0/61 • 28 days
Blood and lymphatic system disorders Bleeding	0.00% 0/64 • 28 days	1.6% 1/61 • Number of events 1 • 28 days
Blood and lymphatic system disorders Pancytopenia	0.00% 0/64 • 28 days	1.6% 1/61 • Number of events 1 • 28 days

Other adverse events

Measure	Placebo n=64 participants at risk Placebo designed to mimic intervention Placebo: Placebo designed to mimic intervention	Intervention n=61 participants at risk Vitamin C Vitamin C: Continuous infusion of vitamin C
Gastrointestinal disorders Loose stools	1.6% 1/64 • Number of events 1 • 28 days	0.00% 0/61 • 28 days
Gastrointestinal disorders Nausea	0.00% 0/64 • 28 days	1.6% 1/61 • Number of events 1 • 28 days
Gastrointestinal disorders Dysphagia	0.00% 0/64 • 28 days	1.6% 1/61 • Number of events 1 • 28 days
Cardiac disorders New or worsening heart failure	1.6% 1/64 • Number of events 1 • 28 days	0.00% 0/61 • 28 days
Cardiac disorders Arrythmia	4.7% 3/64 • Number of events 3 • 28 days	6.6% 4/61 • Number of events 7 • 28 days
Cardiac disorders Elevated Troponin w/o ST elevation	1.6% 1/64 • Number of events 1 • 28 days	0.00% 0/61 • 28 days
Respiratory, thoracic and mediastinal disorders Pleural Effusion	1.6% 1/64 • Number of events 1 • 28 days	0.00% 0/61 • 28 days
Blood and lymphatic system disorders Thrombocytopenia	1.6% 1/64 • Number of events 1 • 28 days	1.6% 1/61 • Number of events 1 • 28 days
Blood and lymphatic system disorders Bleeding event	1.6% 1/64 • Number of events 1 • 28 days	0.00% 0/61 • 28 days
Skin and subcutaneous tissue disorders Maculopapular rash	0.00% 0/64 • 28 days	1.6% 1/61 • Number of events 1 • 28 days

Additional Information

Ronald Reilkoff, MD

University of Minnesota

Phone: 612-624-0999

Email: rreilkof@umn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place