Adrenal Cortical Function and Vitamin A Deficiency in Sepsis
Primary Purpose
Sepsis
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Solumedrol 20mg
Vitamin A 100,000 IU
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Sepsis
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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Solumedrol 20mg
Vitamin A 100,000 IU
Placebo
Arm Description
Solumedrol injection will be given in the vein every 8 hrs. for 7 days.
Vitamin A injection will be given in the arm muscle for 7 days.
Placebo will be given in the vein every 8 hrs. for 7 days or given in the arm muscle for 7 days.
Outcomes
Primary Outcome Measures
28 days mortality
Document the 28 days of mortality
Secondary Outcome Measures
14 day mortality
Mortality at day 14
Number of Secondary Infections
Document the number of secondary infections
Days in ICU
Document the days in ICU
Number of days on ventilator
Document the days on ventilator
Number of days of ventilator adjusted for mortality
Document the number of days of ventilator adjusted for mortality
Number of days on pressor agents
Document the number of days on pressor agents
Number of Days on PPI or H2 blockers
Document the days on PPI or H2 blockers
Number of days of pressor agents corrected for mortality
Document the number of days of pressor agents corrected for mortality
Change in serum albumin concentration
Document the serum albumin concentration
New Onset Renal Failure
Document any new onset renal failure
Serum vitamin A concentration
Document levels of serum vitamin A concentration
Urine Vitamin A Concentration
Document levels of vitamin A concentration in urine
APACHE Score
Calculate and document APACHE score
ACTH Stimulation Test
Efficiency of ACTH stimulation test
Full Information
NCT ID
NCT03152474
First Posted
April 7, 2017
Last Updated
May 15, 2017
Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03152474
Brief Title
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
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
February 1993 (undefined)
Primary Completion Date
January 2000 (Actual)
Study Completion Date
January 2000 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Double Blind Placebo Controlled
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double Blind (to investigator, subject, hospital care team and study team members except for research pharmacist), Randomized, Placebo Controlled Clinical Trial; Placebos were wrapped in foil and coded to prevent identification of study material.
Allocation
Randomized
Enrollment
300 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Solumedrol 20mg
Arm Type
Active Comparator
Arm Description
Solumedrol injection will be given in the vein every 8 hrs. for 7 days.
Arm Title
Vitamin A 100,000 IU
Arm Type
Active Comparator
Arm Description
Vitamin A injection will be given in the arm muscle for 7 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be given in the vein every 8 hrs. for 7 days or given in the arm muscle for 7 days.
Intervention Type
Drug
Intervention Name(s)
Solumedrol 20mg
Other Intervention Name(s)
Methylprednisolone Sodium Succinate
Intervention Description
Dosed Intravenous every 8 hrs.
Intervention Type
Drug
Intervention Name(s)
Vitamin A 100,000 IU
Other Intervention Name(s)
Retinol
Intervention Description
Dosed Intramuscular once daily
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo dosed intravenous every 8 hrs. or Intramuscular once daily.
Primary Outcome Measure Information:
Title
28 days mortality
Description
Document the 28 days of mortality
Time Frame
28 days
Secondary Outcome Measure Information:
Title
14 day mortality
Description
Mortality at day 14
Time Frame
14 days
Title
Number of Secondary Infections
Description
Document the number of secondary infections
Time Frame
Day 28
Title
Days in ICU
Description
Document the days in ICU
Time Frame
Day 14 and Day 28
Title
Number of days on ventilator
Description
Document the days on ventilator
Time Frame
28 days
Title
Number of days of ventilator adjusted for mortality
Description
Document the number of days of ventilator adjusted for mortality
Time Frame
28 days
Title
Number of days on pressor agents
Description
Document the number of days on pressor agents
Time Frame
28 days
Title
Number of Days on PPI or H2 blockers
Description
Document the days on PPI or H2 blockers
Time Frame
28 days
Title
Number of days of pressor agents corrected for mortality
Description
Document the number of days of pressor agents corrected for mortality
Time Frame
28 days
Title
Change in serum albumin concentration
Description
Document the serum albumin concentration
Time Frame
28 days
Title
New Onset Renal Failure
Description
Document any new onset renal failure
Time Frame
Day 14
Title
Serum vitamin A concentration
Description
Document levels of serum vitamin A concentration
Time Frame
baseline and day 14
Title
Urine Vitamin A Concentration
Description
Document levels of vitamin A concentration in urine
Time Frame
baseline and day 14
Title
APACHE Score
Description
Calculate and document APACHE score
Time Frame
Day 1 and Day 14
Title
ACTH Stimulation Test
Description
Efficiency of ACTH stimulation test
Time Frame
Day 1 and Day 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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)
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Only the de-identified study data will be shared with the other researchers.
Citations:
PubMed Identifier
30661700
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.
Results Reference
derived
Learn more about this trial
Adrenal Cortical Function and Vitamin A Deficiency in Sepsis
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