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CompletedNCT03152474Updated May 16, 2017

Adrenal Cortical Function and Vitamin A Deficiency in Sepsis

A Phase 4 interventional study of Solumedrol 20mg and Vitamin A 100,000 IU in Sepsis, sponsored by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center. Completed. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2017-05-16.

Sponsored by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
300
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Sepsis
  • Severe Sepsis
  • Septic Shock

Exclusion criteria

Exclusion Criteria:

  • On glucocorticoids
  • On Vitamin A
  • On any active medical research study
  • Failed ACTH stimulation test (All serum cortisol concentrations \< 20 mg/dl)
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
300 participants (actual)

Study arms

  • Active comparator
    Solumedrol 20mg

    Solumedrol injection will be given in the vein every 8 hrs. for 7 days.

    Drug: Solumedrol 20mg · Other: Placebo

  • Active comparator
    Vitamin A 100,000 IU

    Vitamin A injection will be given in the arm muscle for 7 days.

    Drug: Vitamin A 100,000 IU · Other: Placebo

  • Placebo comparator
    Placebo

    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 · Drug: Vitamin A 100,000 IU

Interventions

  • DrugSolumedrol 20mg

    Dosed Intravenous every 8 hrs.

    Also known as: Methylprednisolone Sodium Succinate

  • DrugVitamin A 100,000 IU

    Dosed Intramuscular once daily

    Also known as: Retinol

  • OtherPlacebo

    Placebo dosed intravenous every 8 hrs. or Intramuscular once daily.

05

What researchers measure

Primary outcomes

  1. 28 days mortality

    Document the 28 days of mortality

    Time frame: 28 days

Secondary outcomes

  1. 14 day mortality

    Mortality at day 14

    Time frame: 14 days

  2. Number of Secondary Infections

    Document the number of secondary infections

    Time frame: Day 28

  3. Days in ICU

    Document the days in ICU

    Time frame: Day 14 and Day 28

  4. Number of days on ventilator

    Document the days on ventilator

    Time frame: 28 days

  5. Number of days of ventilator adjusted for mortality

    Document the number of days of ventilator adjusted for mortality

    Time frame: 28 days

  6. Number of days on pressor agents

    Document the number of days on pressor agents

    Time frame: 28 days

  7. Number of Days on PPI or H2 blockers

    Document the days on PPI or H2 blockers

    Time frame: 28 days

  8. Number of days of pressor agents corrected for mortality

    Document the number of days of pressor agents corrected for mortality

    Time frame: 28 days

  9. Change in serum albumin concentration

    Document the serum albumin concentration

    Time frame: 28 days

  10. New Onset Renal Failure

    Document any new onset renal failure

    Time frame: Day 14

  11. Serum vitamin A concentration

    Document levels of serum vitamin A concentration

    Time frame: baseline and day 14

  12. Urine Vitamin A Concentration

    Document levels of vitamin A concentration in urine

    Time frame: baseline and day 14

  13. APACHE Score

    Calculate and document APACHE score

    Time frame: Day 1 and Day 14

  14. ACTH Stimulation Test

    Efficiency of ACTH stimulation test

    Time frame: Day 1 and Day 8

06

Study locations

No study locations are listed for this record.

07

References and documents

Publications

  • 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. PubMed 30661700 ↗

Individual participant data

Plan to share: Yes — Only the de-identified study data will be shared with the other researchers.

08

Registry details

Key details

Study ID
NCT03152474
Lead sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Responsible party
Sponsor
First posted
May 15, 2017
Start date
Feb 1993
Primary completion
Jan 2000
Completion
Jan 2000
Last update
May 16, 2017

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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