Thiamine, Vitamin C and Hydrocortisone in the Treatment of Septic Shock

A Single Center, Investigator Blinded, Randomized Placebo Control, 24 Month, Parallel Group, Superiority Study to Compare the Efficacy of Thiamine, Vitamin C and Hydrocortisone in the Treatment of Septic Shock.

The purpose of this research study is to determine whether patients who receive thiamine (vitamin B1), vitamin C and hydrocortisone while in septic shock have improved outcomes compared to hydrocortisone alone.

A recently published article "Hydrocortisone, Vitamin C and Thiamine for the treatment of Severe Sepsis and Septic Shock," suggested substantial mortality reduction (78%). We wish to test the hypothesis that mortality reduction is at least 25% in a prospective randomized trial. Other important sub-aims include the testing whether the protocol reduces the time on pressors agents, reduces the trajectory of the SOFA score, or reduces the trajectory of procalcitonin.

Study Overview

• Status: Unknown
• Conditions: Septic Shock
• Intervention / Treatment: Dietary supplement: Thiamine and Vitamin C

Detailed Description

The study has four specific aims. The first is to utilize the Marik protocol published in CHEST to determine mortality reduction in septic shock with thiamine (vitamin B1), vitamin C and hydrocortisone supplementation. The second aim is to determine whether supplementation with thiamine, vitamin C and hydrocortisone reduce time spent on vasopressor support. Thirdly, whether the trajectory of the SOFA score is affected by supplementation with thiamine, hydrocortisone and vitamin C. Fourthly, assess the trajectory of procalcitonin, a laboratory test, in patients treated with the protocol.

This is a single center community based hospital in Southwest Michigan, investigator blinded, randomized placebo controlled trial, 24 month, parallel group, two arm, superiority study with a 1:1 allocation ratio to compare the efficacy of thiamine, vitamin C and hydrocortisone in the treatment of severe sepsis and septic shock. Each arm of the research study will contain 30 patients in order to detect a 25% mortality reduction. Enrollment for this study will be initiated in patients with septic shock that require addition of a second pressor agent. The control arm of our randomized trial will receive a second pressor agent, hydrocortisone and standard of care. If the patient needs additional pressor support or therapy, that will be recorded in the results.

The experimental arm will receive a second pressor agent and hydrocortisone, plus thiamine and vitamin C along with the standard of care. If the patient needs additional pressor support or therapy that will be recorded in the results.

To clarify, both arms will utilize two vasopressor agents, hydrocortisone and supportive care, the experimental group will also receive vitamin C and thiamine.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Recruiting
      • Lakeland Regional Healthcare
      • Contact: Brittany J Haines, D.O, M.P.H; Phone Number: 219-508-1370; Email: bhaines1@lakelandhealth.org
      • Contact: Michelino Mancini, DO, FAOECP; Phone Number: 2699834081; Email: mmancini@lakelandhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of Septic Shock on two vasopressor agents
2. Age between 18-90 years old
3. Ability to provide written informed consent

Exclusion criteria include:

1. Age younger than 18 years old
2. Pregnancy
3. DNR or DNI status with limitations of care, such as "supportive care only"
4. Patients/advocates that request thiamine, vitamin C or hydrocortisone supplementation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Placebo Arm; The control arm of our randomized trial will receive a second pressor agent, hydrocortisone and standard of care to care for septic shock. The IV bags will be blinded by pharmacy. If the patient needs additional pressor support or therapy, the data will be recorded in the results.
Experimental: Thiamine and Vitamin C administration Arm; The experimental arm will receive a second pressor agent and hydrocortisone, plus thiamine and vitamin C along with the standard of care. The IV bags will be blinded by pharmacy. If the patient needs additional pressor support or therapy, the data will be recorded in the results.	Dietary supplement: Thiamine and Vitamin C; Supplementary vitamins for the patient in septic shock

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mortality rate comparison of patients with septic shock at Lakeland Regional Medical Center to the study published in CHEST.	The mortality rate difference between control and experimental arms	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The duration on vasopressor support	Control and Experimental arms will quantify the time requiring vasopressor therapy.	24 months
Quantify the Sequential Organ Failure Assessment score in Septic shock patients requiring vasopressor therapy	Control and experimental arms with both calculate daily Sequential Organ Failure Assessment scores to assess for differences.	24 months

Collaborators and Investigators

• Sponsor: Spectrum Health - Lakeland

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2018
• Primary Completion (Anticipated): February 26, 2020
• Study Completion (Anticipated): February 26, 2020

Study Registration Dates

• First Submitted: February 26, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): May 30, 2018
• Last Update Submitted That Met QC Criteria: May 16, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin B Complex; Ascorbic Acid; Thiamine
• Other Study ID Numbers: MMMC#1576

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No