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Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis

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ClinicalTrials.gov Identifier: NCT00368381
Recruitment Status : Withdrawn (Study closed for PI failure to submit renewal paperwork)
First Posted : August 24, 2006
Last Update Posted : February 13, 2012
Information provided by (Responsible Party):
Audis Bethea, Pharm.D., CAMC Health System

Brief Summary:
The purpose of this study is to determine if the combination of hydrocortisone plus fludrocortisone is more efficacious than hydrocortisone alone in treating adrenal insufficiency in severe sepsis.

Condition or disease Intervention/treatment Phase
Sepsis Adrenal Insufficiency Drug: Hydrocortisone Phase 4

Detailed Description:
Sepsis is a significant cause of morbidity and mortality in critically ill patients in the United States. As evidenced by its increasing prevalence and high mortality rates, sepsis is a complex and difficult syndrome to treat. Current therapeutic management of sepsis includes fluid resuscitation, vasopressor and inotropic support, maintenance of oxygen delivery, drotrecogin alpha, and steroid replacement therapy in patients who are found to have adrenal insufficiency. Studies in septic patients suggest that the administration of stress doses of hydrocortisone alone, or the combination of hydrocortisone plus fludrocortisone promotes an improvement in cardiovascular performance and a quicker resolution of shock symptoms. Current therapeutic guidelines for the treatment of severe sepsis recommend either hydrocortisone alone or combination therapy with hydrocortisone and fludrocortisone as therapeutic options for the treatment of adrenal dysfunction in severe sepsis. This study will help determine which regimen is more efficacious in this patient population.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Blinded, Placebo Controlled Trial of Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis
Study Start Date : September 2006
Actual Primary Completion Date : July 2009
Actual Study Completion Date : September 2009

Arm Intervention/treatment
Active Comparator: Hydrocortision and fludrocortisone
Study is comparing hydrocortisone alone versus the combination of hydrocortisone and fludrocortisone in the treatment of adrenal insufficiency of septic patients.
Drug: Hydrocortisone
Patients randomized to this arm will receive hydrocortisone for the treatment of adrenal insufficiency secondary to sepsis.

Primary Outcome Measures :
  1. All cause mortality [ Time Frame: 28 days ]
    All cause mortality during first 28-days after study randomization.

Secondary Outcome Measures :
  1. Intensive care unit survival, duration of intensive care unit stay, duration of hospitalization, survival to hospital discharge, time to vasopressor withdrawal [ Time Frame: Unable to define ]
    The various secondary endpoints are patient specific serrogate markers of improvement in clinical status. Time frame for these endpoints to occur is patient specific and can not be defined for the entire study population.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males and non-pregnant females > 18 years of age
  • Patients admitted and/or pending admission to the intensive care unit
  • Positive corticotropin stimulation test (Basal cortisol level of ≤ 34 μg/dL with Δ ≤ 9 μg/dL after administration of 250 mg of cosyntropin)

Patient satisfies criteria for severe sepsis Infection - one or more of the following criteria

  • Documented or Suspected - positive culture results (from blood, sputum, urine, etc.)
  • Anti-Infective Therapy - patient is receiving antibiotic, antifungal, or other anti-infective therapy
  • Pneumonia - documentation of pneumonia (x-ray, etc.)
  • WBCs - WBCs found in normally sterile .uid (urine, CSF, etc.)
  • Perforated Viscus - perforation of hollow organ (bowel)

SIRS - two or more of the following

  • Temperature > 38° or < 36°
  • Heart rate > 90 bpm
  • Respiratory rate above 20 breaths per minute
  • WBC > 14,000/mm3 , < 4000/mm3, or >10% Bands

Acute organ dysfunction - one or more of the following

  • Cardiovascular - SBP < 90 mmHg or MAP < 70 mmHg despite 20 mL/kg of fluid resuscitation
  • Respiratory - PaO2/FiO2 ratio < 250, PEEP > 7.5, or require mechanical ventilation
  • Renal - low urine output (eg, <0.5 mL/kg/hr for 1 hour despite 20mL/kg of fluid resuscitation, increased creatinine (>50% increase from baseline) or require acute dialysis
  • Hematologic - low platelet count (< 100,000/mm3) or PT/PTT > upper limit of normal
  • Metabolic - low pH with high lactate (eg, pH < 7.30 and plasma lactate > upper limit of normal
  • Hepatic - liver enzymes > 2x upper limit of normal
  • CNS - altered consciousness or reduced Glasgow Coma Score

Exclusion Criteria:

  • Patients who respond to the short cosyntropin stimulation test(Δ > 9mg/dL)
  • Pregnancy or breast-feeding mother
  • Evidence of acute myocardial infarction, meningitis, pulmonary embolism
  • AIDS (CD4 < 200 cells/mL)
  • Contraindications for corticosteroids
  • Formal indication for corticosteroids (specifically including patients with known adrenal insufficiency)
  • Onset of shock > 24 hours
  • Etomidate administration within the 6 hours preceding randomization
  • Cardiac arrest prior to randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00368381

Sponsors and Collaborators
CAMC Health System
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Principal Investigator: John A Bethea, Pharm.D. Charleston Area Medical Center (CAMC)
Publications of Results:

Other Publications:

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Responsible Party: Audis Bethea, Pharm.D., Clinical Pharmacy Specialist, Trauma/Surgery, CAMC Health System
ClinicalTrials.gov Identifier: NCT00368381    
Other Study ID Numbers: 06-05-1813
First Posted: August 24, 2006    Key Record Dates
Last Update Posted: February 13, 2012
Last Verified: February 2012
Keywords provided by Audis Bethea, Pharm.D., CAMC Health System:
sepsis syndrome
adrenal insufficiency
adrenal cortex hormones
Additional relevant MeSH terms:
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Adrenal Insufficiency
Systemic Inflammatory Response Syndrome
Pathologic Processes
Adrenal Gland Diseases
Endocrine System Diseases
Anti-Inflammatory Agents