Vitamin C and Septic Shock

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled clinical trial to compare Vitamin C versus placebo for patients presenting to the ICU with a diagnosis of septic shock.

Detailed Description
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This is a multi-site, randomized, double-blind, placebo-controlled trial comparing a regimen of moderate-dose (6000 mg per day) Vitamin C supplementation versus placebo for the treatment of patients presenting to the ICU with septic shock. Both groups will continue to receive all other standard of care measures for septic shock as clinically indicated. Groups will be enrolled and receive study drug/placebo for 4 days (96 hours) or until 24 hours post-last pressor dose, whichever is sooner.

Official Title
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Evaluating Vitamin C in Septic Shock: A Randomized Double Blind Placebo Controlled Trial

Conditions
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Septic Shock, Sepsis

Intervention / Treatment
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* Drug: Vitamin C
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Capability to provide written consent from participant or legally authorized representative (LAR) if the participant is unable or incapacitated due to severity of illness. Age ≥ 18 years Septic shock as pragmatically defined as: o Order for intravenous antimicrobials with either procalcitonin > 2 mg/dL within 24 hours of enrollment OR other clinical suspicion of infection or confirmed infection AND Hypotension requiring vasopressor therapy, despite fluid resuscitation of at least 30 cc/kg AND Lactate > 2 mmol/L 24 hr prior to enrollment AND Presence of sepsis defined as equal to or greater than 2 SIRS criteria and/or acute increase in qSOFA score of 2 points or more. SIRS criteria: 1) Temperature greater than 38° or less than 36° Celsius. 2) Heart rate greater than 90 beats per minute. 3) Respiratory rate greater than 20 breaths per minute OR arterial carbon dioxide tension less than 32 mmHg. 4) White blood cell count greater than 12,000 cell/µL, less than 4,000 cells/µL, OR band cells greater than 10% of the total white blood cell population. qSOFA: 1 point each is assigned for: 1) systolic blood pressure below 100, 2) respiratory rate greater than 22, and 3) mental status not at baseline. Exclusion Criteria: • Unable to start infusion within 24 hours of septic shock identification Currently pregnant or breastfeeding Patient to receive comfort measures only Cardiac Arrest Cardiovascular Surgery patients receiving prophylactic peri-operative antibiotics < 48 hours post-operation Participation in another study involving an investigational product within 30 days of the baseline visit Allergy to Vitamin C History of nephrolithiasis History of G6PD deficiency ESRD patients, transplant eligible on dialysis currently taking vitamin C supplementation Clinical course that treating clinician decides would preclude safe participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Placebo<br>Placebo designed to mimic intervention | Drug: Placebo<br>* Placebo designed to mimic intervention<br>|
| Active Comparator: Intervention<br>6000 mg per day Vitamin C supplement | Drug: Vitamin C<br>* Continuous infusion of vitamin C<br>* Other names: ascorbic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With ICU Mortality | Outcome is reported as the number of patients who expired while receiving care in the intensive care unit (ICU). | 28 days | 
| All Cause Mortality at 28 Days | Outcome is reported as the number of participants who have expired at 28 days post intervention | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Vasopressor Therapy | Outcome is reported as the duration in hours of vasopressor therapy post intervention administration | 28 days | 
| Duration of ICU Stay Post Intervention Administration | Outcome is reported as the duration (in days) that participants require care in the intensive care unit (ICU) post intervention administration | 28 days | 
| Time to Lactate Clearance Post Intervention Administration |  | 28 days | 
| Rate of Lactate Clearance Post Intervention Administration | 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. | 24, 48, 72, and 96 hours post intervention | 
| Rate of Procalcitonin Clearance Post Intervention Administration |  | 4 days | 
| Number of Participants With Need for Renal Replacement Therapy | Outcome is reported as the number of participants who require renal replacement therapy | 4 days | 
| Change in Serum Creatinine | Outcome is report as the change in serum creatinine between baseline and 4 days following treatment. Outcome is reported in units of mg/dl. | Baseline and 4 days | 
| Change in Sequential Organ Failure Assessment (SOFA) Score | 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. | Baseline and 4 days | 
| Change in Acute Physiology and Chronic Health Evaluation (APACHE) Scores | 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. | Baseline and 4 days | 
| Total Intravenous Fluid Administered | Outcome is reported as the total volume of intravenous fluid (in liters) administered to participants during 24 hours following the initiation of study treatment. | 24 hours |