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

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ClinicalTrials.gov Identifier: NCT03913468
Recruitment Status : Active, not recruiting
First Posted : April 12, 2019
Last Update Posted : October 4, 2019
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison

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
Septic Shock Ascorbic Acid Deficiency 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.


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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Retrospective
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 : January 1, 2019
Estimated Primary Completion Date : April 1, 2020
Estimated Study Completion Date : April 1, 2020


Group/Cohort 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.



Primary Outcome Measures :
  1. Duration of Vasopressors [ Time Frame: At study conclusion, up to 3 months ]
    Length of time requiring IV vasopressors


Secondary Outcome Measures :
  1. ICU mortality [ Time Frame: At study conclusion, up to 3 months ]
    proportion of patients surviving to ICU discharge

  2. Need for Renal Replacement Therapy [ Time Frame: At study conclusion, up to 3 months ]
    Proportion of patients requiring renal replacement therapy



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients admitted to the ICU to the medical critical care service with a diagnosis of septic shock
Criteria

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

Information from the National Library of Medicine

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): NCT03913468


Locations
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United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
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Principal Investigator: Pierre Kory, MD University of Wisconsin, Madison

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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT03913468     History of Changes
Other Study ID Numbers: 2018-1310
First Posted: April 12, 2019    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Wisconsin, Madison:
ascorbic acid
septic shock
severe sepsis
Additional relevant MeSH terms:
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Shock, Septic
Ascorbic Acid Deficiency
Shock
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Ascorbic Acid
Thiamine
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Nutrients
Growth Substances
Vitamin B Complex