Impact of Hydrocortisone Administration on White Blood Cell Gene Expression in Patients With Severe Sepsis

This study has been completed.
Sponsor:
Collaborators:
University of Toronto
University of Colorado, Denver
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00185783
First received: September 12, 2005
Last updated: April 7, 2011
Last verified: April 2011

September 12, 2005
April 7, 2011
March 2005
November 2006   (final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT00185783 on ClinicalTrials.gov Archive Site
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Impact of Hydrocortisone Administration on White Blood Cell Gene Expression in Patients With Severe Sepsis
Pilot Study of White Blood Cell Gene Expression in Critically Ill Patients With Severe Sepsis and Relative Adrenal Insufficiency After Hydrocortisone Administration

The purpose of this pilot study is to (1) examine the changes in gene expression in patients who suffer from severe sepsis and whose shock (inadequate oxygen delivery to vital organs) state does not respond to fluid and vasopressor administration, (2) to show that our sampling method of isolating RNA provides reliable and consistent data, (3) provide a basis for future gene expression studies in critically ill patients

Severe sepsis is characterized by inadequate perfusion of vital organs due to infection. More than 750,000 cases of severe sepsis occur each year in the United States. Mortality among patients with severe sepsis ranges from 7% to 50%. Initiation of antibiotic therapy within the first hour of diagnosis as well as fluid resuscitation and hemodynamic stabilization are primary goals of therapy.

Steroid administration has been shown to improve outcome in the subset of severe sepsis patients suffering from relative adrenal insufficiency. Although initial studies using high dose short course steroid therapy did not demonstrate efficacy, more recent studies of low dose longer duration hydrocortisone administration demonstrated a significant reduction in mortality at 28 days. The mechanism by which steroid administration affords protection is unclear. We hypothesize that steroid administration changes white blood cell gene and protein expression in severe sepsis patients from an immuno-inflammatory profile to a pattern consistent with healing.

Our first specific aim is to obtain plasma and total cellular RNA from leukocytes in the blood of ten patients admitted to Stanford Medical Center with the diagnosis of severe sepsis and adrenal insufficiency. Significant and distinct variations in whole blood leukocyte gene expression patterns occur depending upon the method of RNA isolation. We will attempt to demonstrate that our sampling method provides reliable and consistent data.

Our second specific aim is to begin an analysis of gene expression patterns in white blood cells before and after steroid administration in patients suffering from severe sepsis with relative adrenal insufficiency. We will use a protocol for assessment of gene expression that was developed by members of our research team.

Observational
Observational Model: Cohort
Time Perspective: Prospective
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Non-Probability Sample

Patients admitted to the Stanford Hospital ICU with Sepsis.

  • Sepsis
  • Relative Adrenal Insufficiency
Drug: Hydrocortisone Administration (Standard of Care Therapy)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
November 2006
November 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Admission Diagnosis of Sepsis
  • Evidence of Relative Adrenal Insufficiency
  • Hypotension (Mean Arterial Pressure less than 60 mm Hg) Refractory to a. Fluid Resuscitation b. Dopamine infusion (greater than 5 micrograms/kg/min) c. Phenylephrine infusion (greater than 1 microgram/kg/min)

Exclusion Criteria:

  • Use of Immunosuppressant Medications
  • Immune Compromised Due to Disease (e.g., HIV infection)
  • Transfusion of Blood Products within the past 7 Days
  • Use of Cytokine Therapy (i.e., G-CSF)
  • History of Bone Marrow Transplantation
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00185783
95230, Stanford IRB Number 4593, Other Grant
Yes
Andrew J. Patterson, M.D., Ph.D., Stanford University
Stanford University
  • University of Toronto
  • University of Colorado, Denver
Principal Investigator: Andrew J Patterson, M.D., Ph.D. Stanford University, Dept. of Anesthesia, Division of Critical Care Medicine
Principal Investigator: Ann Weinacker, M.D., Stanford University, Dept. of Medicine, Div. of Pulmonary and Critical Care Medicine
Stanford University
April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP