Clinical trial NCT00368381: Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis
Official title: A Blinded, Placebo Controlled Trial of Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Sepsis
Adrenal Insufficiency
Keywords: sepsis
septicemia
sepsis syndrome
adrenal insufficiency
adrenal cortex hormones
hydrocortisone
fludrocortisone
Lead sponsor: CAMC Health System
Sponsor class: OTHER
First posted: 2006-08-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: All cause mortality
timeFrame: 28 days
Secondary outcomes:
measure: Intensive care unit survival, duration of intensive care unit stay, duration of hospitalization, survival to hospital discharge, time to vasopressor withdrawal
timeFrame: Unable to define
Other outcomes:
Locations:
Study officials:
affiliation: Charleston Area Medical Center (CAMC)
name: John A Bethea, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
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