Clinical trial NCT03152474: Adrenal Cortical Function and Vitamin A Deficiency in Sepsis
Official title: Adrenal Cortical Function and Vitamin A Deficiency in Sepsis, Severe Sepsis and Septic Shock: Prospective Randomized, Double Blind Placebo Controlled Clinical Trials
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sepsis
Lead sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Sponsor class: OTHER
First posted: 2017-05-15
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double Blind Placebo Controlled
Primary purpose: TREATMENT

Brief summary: The study involves the participant to receive a 250 mcg Cortrosyn (ACTH) Stimulation Test to test the ability of the body to make Cortisol. If the body is not able to make large amount of Cortisol (Delta Cortisol \< 13 mg/dl) from the stimulation test, then the participant will be given additional cortisol like medicine called Solumedrol or matching placebo.

If the body is able to make large amounts of Cortisol (\> 13 mg/dl), then the participant will receive daily shots of Vitamin A for 7 days or matching placebo.

If the participant does not respond to the stimulation test, and meets the criteria for Cortisol deficiency (all 3 cortisol concentrations \< 20 mg/dl), then he/she will screen failed for the study and will be offered hydrocortisone as part of routine care by the treating physician.

Detailed description: The eligible patients will have Sepsis, Severe Sepsis or Septic Shock. The potential subject will be approached for the study participation and if agreed will sign an Inform Consent. Patients unable to give consent, a waiver of consent was used. The participant to receive a Cortrosyn Stimulation Test to test the ability of the body to make Cortisol. The Cortrosyn Stimulation Test involves an injection into the vein in the arm. Two tablespoons of blood is collected just before the injection of Cortrosyn (250 mcg of ACTH) and again 30 minutes and 60 minutes after the injection. The results of test are available about 3 hours after the start of the test. Depending on the results of the test, subject will be either screen failed or will either receive Solumedrol or Vitamin A. Also at the beginning of the study, the amount of water in the subject's body will be measured using a machine called Impedance Monitor.

If the body is not able to make large amount of Cortisol from the stimulation test (delta increase in cortisol \< 13 mg/dl), then the participant will be given additional cortisol like medicine called Solumedrol (20 mg) by injection into a vein every 8 hours for 7 days or matching placebo.

If the body is able to make large amounts of Cortisol (delta cortisol response \> 13 mg/dL), then the participant will receive daily shots of Vitamin A or matching placebo for 7 days by injection into arm muscle. After 1, 3, 8 and 14 days of the study, a blood draw will performed to measure the amount of Vitamin A in the blood. Also, the urine will be collected to measure Vitamin A levels on day 1, 2, 3, 8 and 14. The ACTH stimulation test was repeated on Day 8.

The total amount of blood drawn for the study will be about 18 tablespoons.

If the participant does not respond to the stimulation test, and meets the criteria for Cortisol deficiency (All cortisol concentrations \< 20 mg/dl) , then he/she will screen failed for the study and will be offered 100 mg of hydrocortisone treatment (100 mg IV every 8 hours) as part of routine care by the treating physician.

Eligibility criteria: Inclusion Criteria:

* Sepsis
* Severe Sepsis
* Septic Shock

Exclusion Criteria:

* On glucocorticoids
* On Vitamin A
* On any active medical research study
* Failed ACTH stimulation test (All serum cortisol concentrations \< 20 mg/dl)

Primary outcomes:
measure: 28 days mortality
timeFrame: 28 days
Secondary outcomes:
measure: 14 day mortality
timeFrame: 14 days
measure: Number of Secondary Infections
timeFrame: Day 28
measure: Days in ICU
timeFrame: Day 14 and Day 28
measure: Number of days on ventilator
timeFrame: 28 days
measure: Number of days of ventilator adjusted for mortality
timeFrame: 28 days
measure: Number of days on pressor agents
timeFrame: 28 days
measure: Number of Days on PPI or H2 blockers
timeFrame: 28 days
measure: Number of days of pressor agents corrected for mortality
timeFrame: 28 days
measure: Change in serum albumin concentration
timeFrame: 28 days
measure: New Onset Renal Failure
timeFrame: Day 14
measure: Serum vitamin A concentration
timeFrame: baseline and day 14
measure: Urine Vitamin A Concentration
timeFrame: baseline and day 14
measure: APACHE Score
timeFrame: Day 1 and Day 14
measure: ACTH Stimulation Test
timeFrame: Day 1 and Day 8
Other outcomes:
Locations:
Study officials:
References:
citation: Cherukuri L, Gewirtz G, Osea K, Tayek JA. Vitamin A treatment for severe sepsis in humans; a prospective randomized double blind placebo-controlled clinical trial. Clin Nutr ESPEN. 2019 Feb;29:49-51. doi: 10.1016/j.clnesp.2018.10.011. Epub 2018 Nov 17.