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

Information source: CAMC Health System
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Sepsis; Adrenal Insufficiency

Intervention: Hydrocortisone (Drug)

Phase: Phase 4

Status: Withdrawn

Sponsored by: CAMC Health System

Official(s) and/or principal investigator(s):
John A Bethea, Pharm.D., Principal Investigator, Affiliation: Charleston Area Medical Center (CAMC)


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.

Clinical Details

Official title: A Blinded, Placebo Controlled Trial of Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: All cause mortality

Secondary outcome: Intensive care unit survival, duration of intensive care unit stay, duration of hospitalization, survival to hospital discharge, time to vasopressor withdrawal

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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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


- 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


- 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.

Locations and Contacts

Additional Information

Related publications:

Balk RA. Severe sepsis and septic shock. Definitions, epidemiology, and clinical manifestations. Crit Care Clin. 2000 Apr;16(2):179-92. Review.

Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001 Aug 23;345(8):588-95. Review.

Dellinger RP. Cardiovascular management of septic shock. Crit Care Med. 2003 Mar;31(3):946-55. Review.

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. Review.

Vincent JL, Abraham E, Annane D, Bernard G, Rivers E, Van den Berghe G. Reducing mortality in sepsis: new directions. Crit Care. 2002 Dec;6 Suppl 3:S1-18. Epub 2002 Dec 5. Review.

Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002 Jan 9;287(2):236-40. Review.

Lamberts SW, Bruining HA, de Jong FH. Corticosteroid therapy in severe illness. N Engl J Med. 1997 Oct 30;337(18):1285-92. Review.

Marik PE, Zaloga GP. Adrenal insufficiency in the critically ill: a new look at an old problem. Chest. 2002 Nov;122(5):1784-96. Review.

Annane D. Corticosteroids for septic shock. Crit Care Med. 2001 Jul;29(7 Suppl):S117-20. Review.

Williamson DR, Lapointe M. The hypothalamic-pituitary-adrenal axis and low-dose glucocorticoids in the treatment of septic shock. Pharmacotherapy. 2003 Apr;23(4):514-25. Review.

Shenker Y, Skatrud JB. Adrenal insufficiency in critically ill patients. Am J Respir Crit Care Med. 2001 Jun;163(7):1520-3. Review.

Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003 Feb 20;348(8):727-34. Review.

Starting date: September 2006
Last updated: February 10, 2012

Page last updated: August 23, 2015

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