Therapy With Hydrocortisone, Ascorbic Acid, Thamine in Patients With Sepsis

The Effect of Hydrocortisone-Ascorbic Acid and Thiamine Therapy on the Outcome of Patients With Sepsis: A Prospective Randomized Double-Blinded Controlled Trial

In this study , we suggest that the use of combination of Hydrocortisone, Ascorbic Acid, and Thiamine in patient with sepsis may decrease mortality rate and improve the outcome.

This study will be carried out at SICU of Tanta University hospitals on Patients aged from 18 to 65 years old who will be presented with sepsis that diagnosed according to the surviving sepsis campaign 2016.

Patients who will meet the previous criteria will be enrolled in the study. The patients will be randomized allocated into two groups by the aid of computer generated software of randomization introduced into sealed closed envelops.

All patients will receive the conventional therapy according to the surviving sepsis campaign 2016 and The Surviving Sepsis Campaign Bundle 2018 Update.

The patients will be allocated randomly into one of the following two groups;-. Group I The patients in this group will be managed only according to the surviving sepsis campaign 2016 and the surviving sepsis campaign bundle 2018 update.

The patients will receive 50 ml normal saline I.V within 30 mins / 6 h, 10 ml normal saline I.V / 6 h, 5 ml normal saline I.V / 12 h.

Group II The patients will receive the conventional therapy of sepsis and combined therapy of hydrocortisone (Solucortif® 100 mg , vial, dried powder Pfizer, Egypt) 50 mg diluted in 5 ml normal saline IV / 6 h, ascorbic acid (VITAMIN C-®, Amp, ROTEXMEDICA, Germany, 500mg/5ml) 1.5 gm diluted in 50 ml normal saline IV within 30 min /6 h , and thiamine (Vitamin B1-injektopas®, Ampoule, Germany, 100 mg / 2 ml) 200 mg diluted in 10 ml normal saline IV /12 h The outcome of the patients, the incidence of organ dysfunction will be assessed.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Drug: Normal saline; Drug: Hydrocortisone, Ascorbic acid, Thiamine

Detailed Description

This prospective randomized controlled double-blinded study will be carried out at surgical intensive care units (SICU) in Tanta University Hospitals for a period of 12 months that may be extended after approval from institutional ethical committee.

An informed written consent will be obtained from the patients or patients' relatives.

They will receive an explanation of the purpose of the study and every patient will have a secret code number.

Research results will be only used for scientific purpose. Any unexpected risk/s appearing during the course of research will be clarified to the participants and to the ethical committee on time, however, the patients that will be enrolled in this study have no expected additional risk as we use Hydrocortisone, Ascorbic acid and Thiamin that have minimal side effects.

*Inclusion criteria: Patients aged from 18 to 65 years old who will be presented with sepsis that diagnosed according to the surviving sepsis campaign 2016(21) and The Surviving Sepsis Campaign Bundle 2018 Update.

*Exclusion Criteria:

• Participant or participants' relatives refusal to continue the study.
• Known or suspected allergy to the studied medications.
• Contraindications to the use of vitamin C as renal stones, Alzheimer's disease and Schizophrenia.
• Pre-existing organ failure or dysfunction not related to the presenting sepsis condition.
• Pregnancy.

Patients who will meet the previous criteria will be enrolled in the study. The patients will be randomized allocated into two groups by the aid of computer generated software of randomization introduced into sealed closed envelops.

All patients will receive the conventional therapy according to the surviving sepsis campaign 2016 and The Surviving Sepsis Campaign Bundle 2018 Update.

An intensivist who has no further role in this research work will help in the preparation of the used medications in syringes that will contain medications in group two and normal saline in group one.

(placebo) -I Group The patients in this group will be managed only according to the surviving sepsis campaign 2016 and the surviving sepsis campaign bundle 2018 update.

The patients will receive 50 ml normal saline I.V within 30 mins / 6 h, 10 ml normal saline I.V / 6 h, 5 ml normal saline I.V / 12 h.

Group II The patients will receive the conventional therapy of sepsis and combined therapy of hydrocortisone (Solucortif® 100 mg , vial, dried powder Pfizer, Egypt) 50 mg diluted in 5 ml normal saline IV / 6 h, ascorbic acid (VITAMIN C-®, Amp, ROTEXMEDICA, Germany, 500mg/5ml) 1.5 gm diluted in 50 ml normal saline IV within 30 min /6 h , and thiamine (Vitamin B1-injektopas®, Ampoule, Germany, 100 mg / 2 ml) 200 mg diluted in 10 ml normal saline IV /12 h This combined therapy will be given for 4 days or to the time of discharge if the admission period is less than 4 days.

*Measurements

All data will be collected by intensivists who will be blinded about the study groups. All the patients will be subjected to the following:

1. Demographic data (age, gender, weight, cause of sepsis).
2. 28th day mortality (If the patient will be discharged, data will be collected by phone calls)
3. Sofa score will be recorded daily and compared during the period of the studied drugs administration.
4. Incidence of organ dysfunction during the period of ICU stay.
5. Mean arterial blood pressure will be recorded every 8 hrs and compared during the period of the studied drugs adminstration.
6. Cardiac index will be measured every 8 hrs using Electrical Cardiometry monitor, ICON Cardiotronics, Inc., La Jolla, CA 92307; Osypka Medical GmbH, Berlin,Germany and will be compared between both groups during the period of the studied drugs adminstration.
7. Total dose of vasopressor therapy.
8. Serum lactate level will be measured daily during the period of the studied drugs administration.
9. Serum pocalcitonin level will be measured at time of starting the studied drugs administration and at the end of it.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Tanta, Egypt, 31511
    • Tanta University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged from 18 to 65 years old who will be presented with sepsis that diagnosed according to the surviving sepsis campaign 2016 and The Surviving Sepsis Campaign Bundle 2018 Update

Exclusion Criteria:

• Participant or participants' relatives refusal to continue the study.
• Known or suspected allergy to the studied medications.
• Contraindications to the use of vitamin C as renal stones, Alzheimer's disease and Schizophrenia.
• Pre-existing organ failure or dysfunction not related to the presenting sepsis condition.
• Pregnancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group I; The patients in this group will be managed only according to the surviving sepsis campaign 2016 and the surviving sepsis campaign bundle 2018 update. The patients will receive 50 ml normal saline I.V within 30 mins / 6 h, 10 ml normal saline I.V / 6 h, 5 ml normal saline I.V / 12 h.	Drug: Normal saline; Normal saline
Experimental: Group II; The patients will receive the conventional therapy of sepsis and combined therapy of hydrocortisone (Solucortif® 100 mg , vial, dried powder Pfizer, Egypt) 50 mg diluted in 5 ml normal saline IV / 6 h, ascorbic acid (VITAMIN C-®, Amp, ROTEXMEDICA, Germany, 500mg/5ml) 1.5 gm diluted in 50 ml normal saline IV within 30 min /6 h , and thiamine (Vitamin B1-injektopas®, Ampoule, Germany, 100 mg / 2 ml) 200 mg diluted in 10 ml normal saline IV /12 h This combined therapy will be given for 4 days or to the time of discharge if the admission period is less than 4 days	Drug: Hydrocortisone, Ascorbic acid, Thiamine; Combination of hydrocortisone, ascorbic acid, and thiamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28th day mortality rate.	The incidence of mortality in the first 28 days	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in SOFA score	the incidence of organ dysfunction	28 days
Changes in serum pocalcitonin level	the plasma level of procalcitonin	7 days

Collaborators and Investigators

• Sponsor: Tanta University
• Collaborators: Mostafa Ismail Sharaf; Salah Eldeen Ibrahim Alsherif; Mohamed Mohi El deen Abo El yazeed

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Actual): July 26, 2021
• Study Completion (Actual): July 26, 2021

Study Registration Dates

• First Submitted: November 9, 2019
• First Submitted That Met QC Criteria: November 9, 2019
• First Posted (Actual): November 13, 2019

Study Record Updates

• Last Update Posted (Actual): August 2, 2021
• Last Update Submitted That Met QC Criteria: July 30, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Ascorbic acid; Thiamine; Hydrocortison
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin B Complex; Hydrocortisone; Ascorbic Acid; Thiamine
• Other Study ID Numbers: 33375/09/19

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