Outcomes of Septic Shock Patients Treated With a Metabolic Resuscitation Bundle Consisting of Intravenous Hydrocortisone, Ascorbic Acid and Thiamine.

University of Wisconsin, Madison (Other)
Overall Status
CT.gov ID

Study Details

Study Description

Brief Summary

This is a retrospective chart review that will measure the impact on outcomes in septic shock patients who were resuscitated with a novel combination of medicines called iHAT (intravenous hydrocortisone -ascorbic acid-thiamine). Septic shock patients treated with this combination of drugs over the past two years will be compared with similar, concurrent septic shock patients who were not treated with this drug given that adoption of this therapy has been variable.

Condition or Disease Intervention/Treatment Phase
  • Drug: Intravenous Ascorbic Acid

Detailed Description

The condition of septic shock and multi-organ failure directly results from the rapid consumption of ascorbic acid stores in humans suffering an infection (research in septic patients have demonstrated near uniform deficiency/depletion of ascorbic acid on presentation to ICU's).

This rapidly acquired ascorbic acid deficiency leads to shock and multi-organ failure due to the fact that ascorbic acid is required for humans to produce endogenous vasopressors (hormones that regulate blood pressure) as well as to maintain the function and integrity of the endothelium-the endothelium is the largest organ in the body and is critical in regulating blood pressure and preventing fluid leakage into all organs of the body, a pervasive dysfunction which underlies "multi-organ failure". Oral administration of ascorbic acid, even in high doses, has limited bioavailability (transporter mechanisms in the intestines are limited) and does not lead to appreciable correction of the deficiency, neither in the short term, nor in the critically ill.

In contrast, intravenous administration, in high doses, rapidly achieves not only normal levels, but even supranormal levels.This critical need for intravenous supplementation to treat septic shock was first argued for in 2006 by the European Respiratory Society's "Consensus Committee on Intravenous (Parenteral) Vitamin C" a committee comprised of scientists, researchers, and clinicians studying the role ascorbic acid in sepsis/shock models from all over the world. This was followed by two randomized controlled trials in 2014 showing high efficacy of intravenous ascorbic acid in preventing death in septic shock patients. In 2016, a highly publicized historical control trial further demonstrated a large reduction in vasopressor duration, mortality and renal replacement therapy in a cohort of patients after aggressively correcting ascorbic acid deficiency via the intravenous route showing that multi organ failure and death is immediately prevented in almost all patients. More recently, he has published a study demonstrating the synergistic effects of pairing ascorbic acid with hydrocortisone--endothelial barriers are restored to a greater extent than either agent alone.

Lastly, two trials in the past two years have shown that intravenous thiamine, when systematically provided to the critically ill, independently leads to reduced mortality. Thus, HAT therapy appears to be of high utility in preventing death and multi-organ failure in septic shock. Beyond the above mentioned small, single center observational and randomized controlled trials, no other outcome studies have been done in septic shock patients.

Study Design

Study Type:
Actual Enrollment :
206 participants
Observational Model:
Time Perspective:
Official Title:
Outcomes of Septic Shock Patients Treated With a Metabolic Resuscitation Bundle Consisting of Intravenous Hydrocortisone, Ascorbic Acid and Thiamine.
Actual Study Start Date :
Jan 1, 2019
Actual Primary Completion Date :
Dec 1, 2019
Actual Study Completion Date :
Dec 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Received Ascorbic Acid IV

Per the medical record, consecutive patients admitted to our institutions ICU with a diagnosis of septic shock within the last 3 years, who were treated within the first 24 hours of admission with the combination of IV ascorbic acid, IV thiamine, and IV hydrocortisone, with a duration of 4 days or until patient leaves the ICU.

Drug: Intravenous Ascorbic Acid
1.5 grams IV ascorbic acid q6h, 50 mg IV hydrocortisone q 6 hours, and 200mg IV thiamine BID administered (as documented in medical record)
Other Names:
  • Metabolic Resuscitation
  • HAT therapy
  • Control Group

    Per the medical record, consecutive patients admitted to our institutions ICU with a diagnosis of septic shock within the last 3 years, who did not receive any treatment with IV ascorbic acid.

    Outcome Measures

    Primary Outcome Measures

    1. Duration of Vasopressors [At study conclusion, up to 3 months]

      Length of time requiring IV vasopressors

    Secondary Outcome Measures

    1. ICU mortality [At study conclusion, up to 3 months]

      proportion of patients surviving to ICU discharge

    2. Need for Renal Replacement Therapy [At study conclusion, up to 3 months]

      Proportion of patients requiring renal replacement therapy

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years to 90 Years
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Inclusion Criteria:
    • Admitting Provider in the ICU Patient database must be on the Critical Care Service

    • Primary diagnosis of sepsis listed in the ICU Patient Database

    • Requirement for vasopressors within 24 hours of admission

    • If outside transfer, transfer to TLC occurred within 24 hours of initial presentation

    • Patient remained on Critical Care service for a minimum of 48 hours

    • If treated with iHAT, iHAT started within 36 hours of admission

    • No transition to comfort care occurred within the first 24 hours

    Exclusion Criteria:
    • patients requiring surgical intervention for source control

    • patients transitioned to comfort measures only within 24 hours of admission

    Contacts and Locations


    Site City State Country Postal Code
    1 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53705

    Sponsors and Collaborators

    • University of Wisconsin, Madison


    • Principal Investigator: Pierre Kory, MD, University of Wisconsin, Madison

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    University of Wisconsin, Madison
    ClinicalTrials.gov Identifier:
    Other Study ID Numbers:
    • 2018-1310
    • A534285
    First Posted:
    Apr 12, 2019
    Last Update Posted:
    Sep 14, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Product Manufactured in and Exported from the U.S.:
    Keywords provided by University of Wisconsin, Madison
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 14, 2021