Evaluation of Hydrocortisone, Vitamin C and Thiamine for the Treatment of Septic Shock (HYVITS)
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|ClinicalTrials.gov Identifier: NCT03380507|
Recruitment Status : Recruiting
First Posted : December 21, 2017
Last Update Posted : April 2, 2019
Despite recent medical advances, sepsis and septic shock remain a major cause of death. Sepsis is a syndrome with a wide array of physiologic, pathologic, and biochemical abnormalities.
Several studies have shown vitamin C have decreased the circulating pro-inflammatory cytokines and oxidative stress.Thiamine had favorable effects on pro-inflammatory cytokines, oxidative stress and cellular hypoxia.The use of hydrocortisone in combination with vitamin C will increase the transport of vitamin C into the cells; since the pro inflammatory cytokines have shown to decrease the expression of the sodium-vitamin C transporter-2 (SVCT2) while glucocorticoids increase the SVCT2 expression.
A recent small retrospective study , showed a significant decrease in mortality when patients with severe sepsis and septic shock are treated with a combination of Hydrocortisone, Vitamin C, and Thiamine. Conducting a similar study with a prospective randomized design will give clinicians all over the world more answers and will help clinicians to provide better care to millions of patients using highly safe therapeutic regimen.
The objective of the current study is to explore the clinical benefits of using a combination of hydrocortisone, vitamin C, and thiamine (triple therapy) for the management of septic shock. To achieve this objective, we will compare two alternative treatment strategies, either triple therapy or usual care in patients with septic shock.
First aim: To assess the effectiveness of the triple therapy for septic shock
Second aim: To assess the safety of triple therapy
|Condition or disease||Intervention/treatment||Phase|
|Septic Shock Critical Illness||Drug: Triple therapy group||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||212 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Open label, prospective, randomized, two-arm parallel-group trial|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of Hydrocortisone, Vitamin C and Thiamine for the Treatment of Septic Shock|
|Actual Study Start Date :||March 17, 2018|
|Estimated Primary Completion Date :||April 30, 2019|
|Estimated Study Completion Date :||May 30, 2019|
Experimental: Triple therapy group
Experimental group will receive usual care according to Hamad Medical Corporation Adult Sepsis Care Pathway (CPW 10311, May 2017) PLUS triple therapy.
Triple therapy regimen:
Intravenous vitamin C (1.5 gm q 6 hourly for 4 days or until ICU discharge, whichever is earlier), hydrocortisone (50 mg q 6 hourly for 7 days or until ICU discharge, whichever is earlier, followed by a taper over 3 days) as well as intravenous thiamine (200 mg q 12 hourly for 4 days or until ICU discharge, whichever is earlier).
Drug: Triple therapy group
Refer to arms description
Other Name: Hydrocortisone, Vitamin C and Thiamine
No Intervention: Control group
Control group will receive usual care only according to Hamad Medical Corporation Adult Sepsis Care Pathway (CPW 10311, May 2017).
- Hospital Mortality at 60 days [ Time Frame: 60 days after randomization ]Patients died during hospital admission
- Time to death [ Time Frame: 60 days after randomization ]Time to death after randomization
- Clinical evidence of organ dysfunction [ Time Frame: 72 hours after randomization ]
Change in SOFA* scores from admission to 72 hours
*SOFA score is the Sequential Organ Failure Assessment score which is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems. The score is made of 6 variables, each variable representing an organ system ( respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems). Each organ system score ranges from 0 (normal) to 4 (high degree of dysfunction/failure). The SOFA score ranges from 0 (normal) to 24 (high degree of dysfunction/failure)
- Length of ICU stay [ Time Frame: 60 days after randomization ]Duration the patient stayed in the ICU
- Length of hospital stay [ Time Frame: 60 days after randomization ]Duration the patient stayed in the hospital
- Duration of vasopressor therapy [ Time Frame: 60 days after randomization ]Time to discontinuation of vasopressor therapy and the MAP is more than 65 mmHg
- Lactate clearance [ Time Frame: 72 hours ]Defined as decrease in serum lactate levels over 72 hrs
- Renal replacement therapy for acute kidney injury [ Time Frame: 60 days after randomization ]Patient needed renal replacement therapy for acute kidney injury (Yes or no for each patient in both groups)
- Need for Extracorporeal membrane oxygenation (ECMO) [ Time Frame: 60 days after randomization ]Patient started on ECMO (Yes or no for each patient in both groups)
- Daily mean patient-day weighted blood glucose [ Time Frame: 7 days after randomization ]Average of all blood glucose readings for a specific patient day then averaged across all patients of the arm.
- Incidence of nephrolithiasis [ Time Frame: 4 days after randomization ]Incidence of nephrolithiasis detected on radiological studies or diagnosed by the primary care team
- Incidence of secondary infections [ Time Frame: 60 days after randomization ]Incidence of secondary infections till ICU discharge
- Mechanical ventilator weaning failure [ Time Frame: 60 days after randomization ]Failure to pass a spontaneous breathing trial or the need for reintubation within 48 hours following extubation
- Hypernatremia [ Time Frame: 7 days after randomization ]serum sodium above 145 mEq/L
- Hypokalemia [ Time Frame: 7 days after randomization ]Serum potassium below 3.5 mEq/L
- Hemolysis [ Time Frame: 4 days after randomization ]Patient had hemolysis (Yes or no for each patient in both groups)
- Gastrointestinal (GI) bleeding [ Time Frame: 7 days after randomization ]Patient had GI bleeding (Yes or no for each patient in both groups)
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): NCT03380507
|Contact: Adham Mohamed, PharmDfirstname.lastname@example.org|
|Contact: Mohamed Abdelaty, MDemail@example.com|
|Hamad Medical Corporation||Recruiting|
|Doha, Qatar, 3050|
|Principal Investigator:||Mohamed Abdelaty, MD||Hamad Medical Corporation|
|Principal Investigator:||Adham Mohamed, PharmD||Hamad Medical Corporation|