Outcomes of Septic Shock Patients Treated With a Metabolic Resuscitation Bundle Consisting of Intravenous Hydrocortisone, Ascorbic Acid and Thiamine.
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03913468|
Recruitment Status : Active, not recruiting
First Posted : April 12, 2019
Last Update Posted : October 4, 2019
|Condition or disease||Intervention/treatment|
|Septic Shock Ascorbic Acid Deficiency||Drug: Intravenous Ascorbic Acid|
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|
|Estimated Enrollment :||80 participants|
|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|
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)
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.
- Duration of Vasopressors [ Time Frame: At study conclusion, up to 3 months ]Length of time requiring IV vasopressors
- 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
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
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53705|
|Principal Investigator:||Pierre Kory, MD||University of Wisconsin, Madison|