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Adrenal Cortical Function and Vitamin A Deficiency in Sepsis

Phase 4
Completed
Conditions
Sepsis
Interventions
Drug: Solumedrol 20mg
Drug: Vitamin A 100,000 IU
Other: Placebo
Registration Number
NCT03152474
Lead Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
300
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Solumedrol 20mgSolumedrol 20mgSolumedrol injection will be given in the vein every 8 hrs. for 7 days.
Solumedrol 20mgPlaceboSolumedrol injection will be given in the vein every 8 hrs. for 7 days.
Vitamin A 100,000 IUVitamin A 100,000 IUVitamin A injection will be given in the arm muscle for 7 days.
Vitamin A 100,000 IUPlaceboVitamin A injection will be given in the arm muscle for 7 days.
PlaceboSolumedrol 20mgPlacebo will be given in the vein every 8 hrs. for 7 days or given in the arm muscle for 7 days.
PlaceboVitamin A 100,000 IUPlacebo will be given in the vein every 8 hrs. for 7 days or given in the arm muscle for 7 days.
Primary Outcome Measures
NameTimeMethod
28 days mortality28 days

Document the 28 days of mortality

Secondary Outcome Measures
NameTimeMethod
Days in ICUDay 14 and Day 28

Document the days in ICU

Number of days on ventilator28 days

Document the days on ventilator

Number of days of ventilator adjusted for mortality28 days

Document the number of days of ventilator adjusted for mortality

Number of days on pressor agents28 days

Document the number of days on pressor agents

14 day mortality14 days

Mortality at day 14

Number of Secondary InfectionsDay 28

Document the number of secondary infections

Number of Days on PPI or H2 blockers28 days

Document the days on PPI or H2 blockers

Number of days of pressor agents corrected for mortality28 days

Document the number of days of pressor agents corrected for mortality

Change in serum albumin concentration28 days

Document the serum albumin concentration

New Onset Renal FailureDay 14

Document any new onset renal failure

Serum vitamin A concentrationbaseline and day 14

Document levels of serum vitamin A concentration

Urine Vitamin A Concentrationbaseline and day 14

Document levels of vitamin A concentration in urine

APACHE ScoreDay 1 and Day 14

Calculate and document APACHE score

ACTH Stimulation TestDay 1 and Day 8

Efficiency of ACTH stimulation test

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