Steroids, Thiamine and Ascorbic Acid in Septic Shock

Septic Shock Clinical Trial

— STASIS  

Official title:

Steroids, Thiamine and Ascorbic Acid Supplementation in Septic Shock (STASIS): A Prospective Crossover Randomized Controlled Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04134403
• Other study ID #: STASIS
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: December 1, 2019
• Est. completion date: December 1, 2020

Study information

• Verified date: October 2019
• Source: Baqiyatallah Medical Sciences University
• Contact: Amir Vahedian-Azimi, PhD
• Phone: +98 919 6017 138
• Email: amirvahedian63[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this project is to determine if in patients admitted to the hospital with septic shock (population), does treatment with a bundle including hydrocortisone, thiamine, and ascorbic acid improve in-hospital or 28-day mortality (primary outcomes) or surrogate markers of illness severity including: (1) ICU or hospital length-of-stay, (2) duration of invasive mechanical ventilation, (3) duration of vasopressor administration, (4) incidence and severity of ICU delirium, and (5) illness severity (secondary outcomes).

Description:

This trial is designed as a multi-center prospective, double-blinded, randomized controlled study. The objective of this project is to determine if in patients admitted to the hospital with septic shock (population), does treatment with a bundle including hydrocortisone, thiamine, and ascorbic acid improve in-hospital or 28-day mortality (primary outcomes) or surrogate markers of illness severity including: (1) ICU or hospital length-of-stay, (2) duration of invasive mechanical ventilation, (3) duration of vasopressor administration, (4) incidence and severity of ICU delirium, and (5) illness severity (secondary outcomes). The calculated sample size is 80. Subjects will be followed for 28 days or until hospital discharge.

Patients eligible for inclusion must be admitted with septic shock (as defined by SEPSIS-3) requiring vasopressors to maintain MAP ≥ 65 AND serum lactate level >2 mmol/L after adequate fluid resuscitation (generally recognized at 30 ml/kg crystalloid unless contraindicated as deemed by treating clinician) within the first three hours.

The exclusion criteria are: age < 18 years, pregnant, patients with limitation of care (i.e. do not resuscitate [DNR]), known Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency, and vasopressor use for > 24 hours prior to study enrollment.

Patients in Arm 1 will randomized to receive usual care + hydrocortisone, thiamine and ascorbic acid. Arm 2 will be randomized to receive usual care alone. Crossover is not allowed. If a patient is randomized into study Arm 2, the treating physician may decide to administer study medications if they feel it is in the best interest of the patient. In this case the patient will continue to be analyzed in their assigned arm on an intention to treat basis. Source of participants will be in-hospital and Emergency Department patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: December 1, 2020
• Est. primary completion date: November 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Septic shock admitted to the ICU within 24 hours as defined by SEPSIS-3

• SEPSIS-3 defines septic shock as sepsis with the following criteria despite adequate fluid resuscitation:

• Vasopressor required to maintain MAP = 65 AND

• Serum lactate level >2.0 mmol/L

• Age = 18 years

• Non-pregnant

• Ability to consent with medical capacity or legally authorized representative (LAR) consent

Exclusion Criteria:

• Age < 18 years

• Pregnant defined by negative serum HCG in all females

• Patients with limitation of care (i.e. DNR)

• Known G6PD deficiency

• Excluding primary admission diagnosis including the following:

• Acute stroke

• Acute coronary syndrome

• Active gastrointestinal bleed

• Burn

• Trauma

• Prisoners

• >1 episode of sepsis in hospital admission

• Vasopressor use prior to randomization for more than 24 hours

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Drug:
• STASIS
Hydrocortisone sodium succinate, 50 mg, every 6 hours, 7 days or until ICU discharge Thiamine, 200 mg, every 12 hours, 4 days or until ICU discharge Ascorbic acid, 1,500 mg, every 6 hours, 4 days or until ICU discharge

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Baqiyatallah Medical Sciences University	Hamadan University of Medical Science, Tehran University of Medical Sciences

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In-hospital or 28-day mortality rate	To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care versus standard care in septic shock confers an in-hospital and 28-day mortality benefit	28 days or discharge (whichever comes first)
Secondary	Illness Severity (Change in SOFA Score)	To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers more rapid improvements in illness severity	72 hours
Secondary	Hospital length-of-stay ICU LOS Duration of intubation	To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers improved hospital length-of-stay metrics	1 year or discharge (whichever comes first)
Secondary	ICU length-of-stay	To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers improved ICU length-of-stay metrics	90 days or discharge (whichever comes first)
Secondary	Vasopressor duration (days)	To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock confers improvement in vasopressor requirements	28 days or discharge (whichever comes first)
Secondary	ICU delerium (CAM-ICU score)	To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the incidence or severity of ICU delerium	28 days or discharge (whichever comes first)
Secondary	Mechanical ventilation	To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the incidence or duration of invasive mechanical ventilation.	28 days or discharge (whichever comes first)
Secondary	Cardiac arrest	To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the incidence of cardiac arrest or need for cardiopulmonary resuscitation	28 days or discharge (whichever comes first)
Secondary	Renal replacement therapy	o determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the incidence of cardiac arrest or need for renal replacement therapy.	28 days or discharge (whichever comes first)
Secondary	C-reactive protein	To determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the biochemical profiling in septic patients including a more rapid improvement in C-reactive protein	28 days or discharge (whichever comes first)
Secondary	Procalcitonin	o determine if the addition of hydrocortisone, thiamine and ascorbic acid to standard care in septic shock changes the biochemical profiling in septic patients including a more rapid improvement in procalcitonin.	28 days or discharge (whichever comes first)