Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS)
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|ClinicalTrials.gov Identifier: NCT03509350|
Recruitment Status : Completed
First Posted : April 26, 2018
Last Update Posted : March 18, 2020
|Condition or disease||Intervention/treatment||Phase|
|Sepsis||Drug: Vitamin C Drug: Thiamine Drug: Hydrocortisone Drug: Vitamin C Placebo Drug: Thiamine Placebo Drug: Hydrocortisone Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||501 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Supportive Care|
|Official Title:||A Multi-center, Randomized, Placebo-controlled, Double-blind, Adaptive Clinical Trial of Vitamin C, Thiamine and Steroids as Combination Therapy in Patients With Sepsis.|
|Actual Study Start Date :||August 22, 2018|
|Actual Primary Completion Date :||August 22, 2019|
|Actual Study Completion Date :||January 29, 2020|
Experimental: Treatment Protocol
Participants randomized to the treatment protocol will receive the VICTAS Intervention, consisting of intravenous vitamin C, thiamine, and hydrocortisone for four days or until ICU discharge.
Drug: Vitamin C
Intravenous vitamin C (1.5 grams every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Ascorbic acid
Intravenous thiamine (100 mg every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Thiamine hydrochloride
Intravenous hydrocortisone (50 mg every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Hydrocortisone sodium succinate
Placebo Comparator: Control Protocol
A placebo to match the VICTAS intervention will be administered for four days or until ICU discharge. During the treatment period, if an indication for steroids exist, the treating physicians are permitted to initiate open-label corticosteroid therapy based on local practice and international guidelines. If this occurs, the hydrocortisone/placebo will be withheld and subjects will be started on open-label corticosteroids.
Drug: Vitamin C Placebo
A placebo to match intravenous vitamin C (1.5 grams every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Placebo
Drug: Thiamine Placebo
A placebo to match intravenous thiamine (100 mg every 6 hours) will be administered for 4 days or until ICU discharge.
Other Name: Placebo
Drug: Hydrocortisone Placebo
A placebo to match intravenous hydrocortisone (50 mg every 6 hours) will be administered for 4 days or until ICU discharge. Steroids will be used when clinically indicated.
Other Name: Placebo
- Vasopressor and ventilator-free days (VVFD) [ Time Frame: Day 30 ]The primary outcome measure is VVFD at 30 days (+/-3 days) after randomization. Vasopressor and ventilator-free days will be determined by recording all start and stop days of these measures.
- Mortality at 30 days [ Time Frame: Day 30 ]The number of participants who did not survive until Day 30 will be compared between study arms.
- Intensive Care Unit (ICU) Mortality [ Time Frame: Day 30 ]The number of participants who die while in the ICU will be compared between study arms.
- Mortality at 180 Days [ Time Frame: Day 180 ]The number of participants who did not survive until Day 180 will be compared between study arms.
- Length of ICU Stay [ Time Frame: Day 30 ]The number of days in the ICU will be compared between study arms.
- Length of Hospital Stay [ Time Frame: Day 30 ]The number of days in the hospital will be compared between study arms.
- Digit Span Test Score [ Time Frame: Day 180 ]The digit span test will be used to assesses attention. 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 amount of numbers the participant was able to remember in each test. Higher scores indicate greater ability to pay attention and to remember sequences.
- Delirium Telephone Confusion Assessment Method (CAM) [ Time Frame: Day 180 ]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.
- Hayling Test Score [ Time Frame: Day 180 ]Executive function will be 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.
- Controlled Oral Word Association Test (COWAT) Score [ Time Frame: Day 180 ]Language will be 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.
- Wechsler Memory Scale IV - Paragraph Recall Score [ Time Frame: Day 180 ]Memory will be assessed with the Paragraph Recall from the Wechsler Memory Scale IV. Participants listen to two short paragraphs and are asked to recall details from each story immediately and after 30 minutes. Scores represent the number of correctly remembered details. Total scores for each recall time period (immediate and after 30 minutes) range from 0 to 25 with higher scores reflecting better memory.
- Telephone Interview for Cognitive Status (TICS) [ Time Frame: 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.
- Wechsler Adult Intelligence Scale (WAIS)-IV Similarities Score [ Time Frame: Day 180 ]Reasoning will be assessed with the WAIS-IV Similarities instrument. Participants are 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.
- Katz Index of Independence in Activities of Daily Living (ADL) Score [ Time Frame: Day 180 ]Activities of daily living will be 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.
- Employment Questionnaire [ Time Frame: Day 180 ]The Employment Questionnaire is a brief measure of the participant's employment history and ability or capacity to work. There is not a summary score for this qualitative questionnaire.
- Functional Activities Questionnaire (FAQ) Score [ Time Frame: Day 180 ]Instrumental activities of daily living will be 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.
- Patient-Reported Outcomes Measurement Information System (PROMIS) Depression 6 [ Time Frame: Day 180 ]Depression will be 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.
- Posttraumatic Stress Disorder - 8 (PTSD-8) [ Time Frame: Day 180 ]Posttraumatic Stress Disorder (PTSD) will be assessed with the Posttraumatic Stress Disorder - 8 instrument. The PTSD-8 includes 8 items which are answered on a 4 point scale where 1 = not at all and 4 = all of the time. Total scores range from 8 to 32 where higher scores indicate greater symptoms of PTSD.
- EuroQol, 5 dimension (EQ5D) [ Time Frame: Day 180 ]Quality of life will be assessed with the EuroQol, 5 dimension (EQ5D) questionnaire. The EQ5D asks about 5 dimensions of health (mobility, self-care, usual activities, pain, and depression). These 5 items are assessed on a scale from 1 to 5 where 1 =no problems and 5 = extremely problematic. Total raw scores range from 5 to 25 where higher scores indicate lower quality of life. The questionnaire also includes a visual analog scale where respondents rate their current health; 0 = worst health imaginable and 100 = best health imaginable.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03509350
|Principal Investigator:||Jonathan Sevransky, MD, MHS||Emory University|