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

Phase 4

Withdrawn

• Conditions: Sepsis; Adrenal Insufficiency
• Interventions: Drug: Hydrocortisone

• Registration Number: NCT00368381
• Lead Sponsor: 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.

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.

Study Timeline

• Study First Submitted: 2006-08-23
• Study First Submitted QC: 2006-08-23
• Study First Posted: 2006-08-24
• Study Start: 2006-09
• Primary Completion: 2009-07
• Study Completion: 2009-09
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-10
• Last Update Posted: 2012-02-13

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hydrocortision and fludrocortisone	Hydrocortisone	Study is comparing hydrocortisone alone versus the combination of hydrocortisone and fludrocortisone in the treatment of adrenal insufficiency of septic patients.

Primary Outcome Measures

Name	Time	Method
All cause mortality	28 days	All cause mortality during first 28-days after study randomization.

Secondary Outcome Measures

Name	Time	Method
Intensive care unit survival, duration of intensive care unit stay, duration of hospitalization, survival to hospital discharge, time to vasopressor withdrawal	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.