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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 : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date February 6, 2019
First Posted Date April 12, 2019
Last Update Posted Date December 3, 2019
Actual Study Start Date January 1, 2019
Estimated Primary Completion Date April 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 11, 2019)
Duration of Vasopressors [ Time Frame: At study conclusion, up to 3 months ]
Length of time requiring IV vasopressors
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: April 11, 2019)
  • ICU mortality [ Time Frame: At study conclusion, up to 3 months ]
    proportion of patients surviving to ICU discharge
  • Need for Renal Replacement Therapy [ Time Frame: At study conclusion, up to 3 months ]
    Proportion of patients requiring renal replacement therapy
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Outcomes of Septic Shock Patients Treated With a Metabolic Resuscitation Bundle Consisting of Intravenous Hydrocortisone, Ascorbic Acid and Thiamine.
Official Title Outcomes of Septic Shock Patients Treated With a Metabolic Resuscitation Bundle Consisting of Intravenous Hydrocortisone, Ascorbic Acid and Thiamine.
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.
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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients admitted to the ICU to the medical critical care service with a diagnosis of septic shock
Condition
  • Septic Shock
  • Ascorbic Acid Deficiency
Intervention 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
Study Groups/Cohorts
  • 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.
    Intervention: Drug: Intravenous Ascorbic Acid
  • 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Estimated Enrollment
 (submitted: April 11, 2019)
80
Original Estimated Enrollment Same as current
Estimated Study Completion Date April 1, 2020
Estimated Primary Completion Date April 1, 2020   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03913468
Other Study ID Numbers 2018-1310
A534285 ( Other Identifier: UW, Madison )
SMPH/MEDICINE/PULMON MED ( Other Identifier: UW, Madison )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University of Wisconsin, Madison
Study Sponsor University of Wisconsin, Madison
Collaborators Not Provided
Investigators
Principal Investigator: Pierre Kory, MD University of Wisconsin, Madison
PRS Account University of Wisconsin, Madison
Verification Date December 2019