Trial Outcomes & Findings for Vitamin C, Thiamine, and Steroids in Sepsis (NCT NCT03509350)

NCT ID: NCT03509350

Last Updated: 2021-04-13

Results Overview

The primary outcome measure is VVFD in the first 30 days after the start of treatment. The endpoint was recorded to the nearest day. Participants who died are scored zero days, even if there was a period during which the participant was alive and free of vasopressors and mechanical ventilation. Participants who must return to ventilation and/or vasopressors had their counters reset at zero days.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 501 participants
• Primary outcome timeframe: Up to Day 30
• Results posted on: 2021-04-13

Participant Flow

Participant enrollment began on August 22, 2018. Follow-up for the primary outcome measure was completed on August 22, 2019 and follow up for the secondary outcome measures was completed on January 29, 2020. Participants were recruited from multiple sites in the United States of America.

Participant milestones

Measure	Treatment Protocol Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Overall Study STARTED	252	249
Overall Study COMPLETED	252	247
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Treatment Protocol Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Vitamin C, Thiamine, and Steroids in Sepsis

Baseline characteristics by cohort

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.	Total n=501 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	148 Participants n=93 Participants	143 Participants n=4 Participants	291 Participants n=27 Participants
Age, Categorical >=65 years	104 Participants n=93 Participants	106 Participants n=4 Participants	210 Participants n=27 Participants
Age, Continuous	62 years n=93 Participants	61 years n=4 Participants	62 years n=27 Participants
Sex: Female, Male Female	113 Participants n=93 Participants	115 Participants n=4 Participants	228 Participants n=27 Participants
Sex: Female, Male Male	139 Participants n=93 Participants	134 Participants n=4 Participants	273 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=93 Participants	24 Participants n=4 Participants	56 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	211 Participants n=93 Participants	215 Participants n=4 Participants	426 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=93 Participants	10 Participants n=4 Participants	19 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	70 Participants n=93 Participants	80 Participants n=4 Participants	150 Participants n=27 Participants
Race (NIH/OMB) White	149 Participants n=93 Participants	135 Participants n=4 Participants	284 Participants n=27 Participants
Race (NIH/OMB) More than one race	33 Participants n=93 Participants	34 Participants n=4 Participants	67 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	252 Participants n=93 Participants	249 Participants n=4 Participants	501 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to Day 30

Population: This analysis uses an intent-to-treat (ITT) analysis set, which includes all participants who enrolled in the study.

The primary outcome measure is VVFD in the first 30 days after the start of treatment. The endpoint was recorded to the nearest day. Participants who died are scored zero days, even if there was a period during which the participant was alive and free of vasopressors and mechanical ventilation. Participants who must return to ventilation and/or vasopressors had their counters reset at zero days.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Vasopressor and Ventilator-free Days (VVFD)	25 days Interval 0.0 to 29.0	26 days Interval 0.0 to 28.0

SECONDARY outcome

Timeframe: Day 30

The number of participants who did not survive until Day 30 is compared between study arms.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Mortality at 30 Days	56 Participants	60 Participants

SECONDARY outcome

Timeframe: Day 30

The number of participants who died while in the ICU is compared between study arms.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Intensive Care Unit (ICU) Mortality	52 Participants	49 Participants

SECONDARY outcome

Timeframe: Day 180

The number of participants who did not survive until Day 180 is compared between study arms.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Mortality at 180 Days	102 Participants	94 Participants

SECONDARY outcome

Timeframe: Day 30

The number of days that participants were in the ICU is compared between study arms.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Length of ICU Stay	6.7 days Standard Deviation 7.3	6.4 days Standard Deviation 6.9

SECONDARY outcome

Timeframe: Day 30

The number of days that participants were in the hospital is compared between study arms.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Length of Hospital Stay	12.6 days Standard Deviation 10	13.5 days Standard Deviation 25.7

SECONDARY outcome

Timeframe: Day 180

The Digit Span Test is used to assesses attention. In the Digit Span Test, participants are read a series of numbers and are asked to repeat them back in the same order. The Digit Span test is scored by the number of digits the participant is able to remember in each test. Higher scores indicate greater ability to pay attention and to remember sequences. The average adult can remember about 7 numbers, plus or minus two, without making an error.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Digit Span Test Score	8.3 numbers recalled Standard Deviation 3.1	9.5 numbers recalled Standard Deviation 3.8

SECONDARY outcome

Timeframe: Day 180

Population: Telephone data are available only on 168 participants

The Telephone CAM evaluates dementia with 9-items, where additional questions are asked if symptoms are present. Rather than providing a summary score, if participants exhibit signs of a change in mental status which fluctuates and they experience inattention, along with disorganized thinking or altered level of consciousness, delirium is suggested.

Outcome measures

Measure	Treatment Protocol n=86 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=82 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Number of Participants With Delirium Assessed With the DeliriumTelephone Confusion Assessment Method (CAM)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 180

Executive function is assessed with the Hayling Test. The Hayling Test includes two parts of 15 items each where participants complete sentences by providing the missing word. The test is scored as the amount of time it takes, in seconds, to recite a correct response and the appropriateness of the response (in Part 2). Scaled scores range from 1 to 10 where 1 = impaired, 6 = average, and 10 = very superior.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Hayling Test Score	4.2 units on a scale Standard Deviation 1.9	4.2 units on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: Day 180

Language is assessed with the Controlled Oral Word Association Test (COWAT). Participants generate words beginning with selected letters within 60 seconds. Generating a higher number of words indicates greater language skills.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Controlled Oral Word Association Test (COWAT) Score	40 words Standard Deviation 11	40 words Standard Deviation 11

SECONDARY outcome

Timeframe: Day 180

Memory is assessed with the Logical Memory subtest from the Wechsler Memory Scale III. Participants listened to two short paragraphs and were asked to recall details from each story after 30 minutes. Scores represent the number of correctly remembered details. Total scores range from 0 to 25 with higher scores reflecting better memory.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Wechsler Memory Scale III - Delayed Recall Logical Memory Score	6.9 correct story details Standard Deviation 2.8	8.1 correct story details Standard Deviation 3.2

SECONDARY outcome

Timeframe: Day 180

The Telephone Interview for Cognitive Status (TICS) is an 11-item instrument assessing orientation. Correct responses to the items are scored in a variety of ways, depending on how much of the response is correct. Total scores range from 0 to 41 with higher scores indicating increased cognitive orientation.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Telephone Interview for Cognitive Status (TICS)	30.6 score on a scale Standard Deviation 4.9	31.2 score on a scale Standard Deviation 5.2

SECONDARY outcome

Timeframe: Day 180

Reasoning is assessed with the WAIS-IV Similarities instrument. Participants were asked to explain how two words are alike. Responses are scored according to how correct they are, with a score of 0 for incorrect answers. After 3 consecutive scores of 0 the survey is stopped. Total raw scores vary depending on the number of word pairs presented. Higher scores indicate better performance. Scores will be compared between study arms.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Wechsler Adult Intelligence Scale (WAIS)-IV Similarities Score	7.7 score on a scale Standard Deviation 3.3	8.2 score on a scale Standard Deviation 3.2

SECONDARY outcome

Timeframe: Day 180

Activities of daily living is assessed with the Katz ADL instrument. The Katz ADL has 6 items asking if participants can perform daily tasks independently. Responses are scored as 1 = yes and 0 = no. Total scores range from 0 to 6 with higher scores indicating greater independence.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Katz Index of Independence in Activities of Daily Living (ADL) Score	2.8 score on a scale Standard Deviation 3.9	2.4 score on a scale Standard Deviation 3.6

SECONDARY outcome

Timeframe: Day 180

Population: This analysis includes participants who completed the Employment Questionnaire.

The Employment Questionnaire is a brief measure of the participant's employment history and ability or capacity to work. The number of participants who indicated being employed are presented here.

Outcome measures

Measure	Treatment Protocol n=99 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=96 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Number of Participants Employed	17 Participants	25 Participants

SECONDARY outcome

Timeframe: Day 180

Instrumental activities of daily living is assessed with the Functional Activities Questionnaire (FAQ). The FAQ includes 10 items which are scored on a scale from 0 to 3 where 0 = normal and 3 = dependent. Total scores range from 0 to 30 and lower scores indicate that the respondent is able to perform daily activities. A score of 9 (where the person is dependent in 3 activities) is used as a cut-point indicating impairments with functioning.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Functional Activities Questionnaire (FAQ) Score	9.5 score on a scale Standard Deviation 10.8	7.7 score on a scale Standard Deviation 9.2

SECONDARY outcome

Timeframe: Day 180

Depression is assessed with the PROMIS Depression 6 instrument. This tool includes 6 items with response options on a scale of 1 to 5. Total raw scores range from 6 to 30 with higher scores indicating greater symptoms of depression.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Patient-Reported Outcomes Measurement Information System (PROMIS) Depression 6	11.9 score on a scale Standard Deviation 6.3	11.9 score on a scale Standard Deviation 5.9

SECONDARY outcome

Timeframe: Day 180

Posttraumatic Stress Disorder (PTSD) is assessed with the Posttraumatic Stress Disorder - 8 instrument. The PTSD-8 includes 8 items which are answered on a 4 point scale where 01 = not at all and 3 = all of the time. Total scores range from 0 to 24 where higher scores indicate greater symptoms of PTSD.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Posttraumatic Stress Disorder-8 (PTSD-8) Score	5.7 score on a scale Standard Deviation 5.8	5.2 score on a scale Standard Deviation 5.1

SECONDARY outcome

Timeframe: Day 180

Quality of life is assessed with the Visual Analog Scale of the EuroQol, 5 dimension (EQ-5D) questionnaire. The EQ-5D asks about 5 dimensions of health (mobility, self-care, usual activities, pain, and depression). The questionnaire includes a visual analog scale where respondents rate their current health where 0 = worst health imaginable and 100 = best health imaginable.

Outcome measures

Measure	Treatment Protocol n=252 Participants Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 Participants Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
EuroQol, 5 Dimension (EQ-5D) Visual Analog Scale Score	66 units on a scale Standard Deviation 22	67 units on a scale Standard Deviation 22

Adverse Events

Treatment Protocol

Serious events: 0 serious events

Other events: 2 other events

Deaths: 102 deaths

Control Protocol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 94 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment Protocol n=252 participants at risk Participants randomized to the treatment protocol received the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.	Control Protocol n=249 participants at risk Participants in the control group received a placebo to match the VICTAS intervention, which was administered for four days or until ICU discharge.
Blood and lymphatic system disorders Hemorrhagic shock due to hemolysis	0.40% 1/252 • Number of events 1 • Adverse events potentially associated with the study treatment and serious adverse events were monitored from the time of randomization up to Day 30. Mortality was recorded from the time of randomization up to Day 180. Adverse events that were not considered serious or potentially associated with the treatment were not recorded.	0.00% 0/249 • Adverse events potentially associated with the study treatment and serious adverse events were monitored from the time of randomization up to Day 30. Mortality was recorded from the time of randomization up to Day 180. Adverse events that were not considered serious or potentially associated with the treatment were not recorded.
Renal and urinary disorders Worsening of renal function	0.40% 1/252 • Number of events 1 • Adverse events potentially associated with the study treatment and serious adverse events were monitored from the time of randomization up to Day 30. Mortality was recorded from the time of randomization up to Day 180. Adverse events that were not considered serious or potentially associated with the treatment were not recorded.	0.00% 0/249 • Adverse events potentially associated with the study treatment and serious adverse events were monitored from the time of randomization up to Day 30. Mortality was recorded from the time of randomization up to Day 180. Adverse events that were not considered serious or potentially associated with the treatment were not recorded.

Additional Information

Jon Sevransky MD, MHS

Emory University

Phone: 404-778-5734

Email: jonathan.sevransky@emoryhealthcare.org

Results disclosure agreements

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