Adrenal Cortical Function and Vitamin A Deficiency in Sepsis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Adrenal Cortical Function and Vitamin A Deficiency in Sepsis, Severe Sepsis and Septic Shock: Prospective Randomized, Double Blind Placebo Controlled Clinical Trials

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Solumedrol 20mg
* Drug: Vitamin A 100,000 IU
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double Blind Placebo Controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Solumedrol 20mg<br>Solumedrol injection will be given in the vein every 8 hrs. for 7 days. | Drug: Solumedrol 20mg<br>* Dosed Intravenous every 8 hrs.<br>* Other names: Methylprednisolone Sodium Succinate;Other: Placebo<br>* Placebo dosed intravenous every 8 hrs. or Intramuscular once daily.<br>|
| Active Comparator: Vitamin A 100,000 IU<br>Vitamin A injection will be given in the arm muscle for 7 days. | Drug: Vitamin A 100,000 IU<br>* Dosed Intramuscular once daily<br>* Other names: Retinol;Other: Placebo<br>* Placebo dosed intravenous every 8 hrs. or Intramuscular once daily.<br>|
| Placebo Comparator: Placebo<br>Placebo will be given in the vein every 8 hrs. for 7 days or given in the arm muscle for 7 days. | Drug: Solumedrol 20mg<br>* Dosed Intravenous every 8 hrs.<br>* Other names: Methylprednisolone Sodium Succinate;Drug: Vitamin A 100,000 IU<br>* Dosed Intramuscular once daily<br>* Other names: Retinol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 days mortality | Document the 28 days of mortality | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 14 day mortality | Mortality at day 14 | 14 days | 
| Number of Secondary Infections | Document the number of secondary infections | Day 28 | 
| Days in ICU | Document the days in ICU | Day 14 and Day 28 | 
| Number of days on ventilator | Document the days on ventilator | 28 days | 
| Number of days of ventilator adjusted for mortality | Document the number of days of ventilator adjusted for mortality | 28 days | 
| Number of days on pressor agents | Document the number of days on pressor agents | 28 days | 
| Number of Days on PPI or H2 blockers | Document the days on PPI or H2 blockers | 28 days | 
| Number of days of pressor agents corrected for mortality | Document the number of days of pressor agents corrected for mortality | 28 days | 
| Change in serum albumin concentration | Document the serum albumin concentration | 28 days | 
| New Onset Renal Failure | Document any new onset renal failure | Day 14 | 
| Serum vitamin A concentration | Document levels of serum vitamin A concentration | baseline and day 14 | 
| Urine Vitamin A Concentration | Document levels of vitamin A concentration in urine | baseline and day 14 | 
| APACHE Score | Calculate and document APACHE score | Day 1 and Day 14 | 
| ACTH Stimulation Test | Efficiency of ACTH stimulation test | Day 1 and Day 8 |