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

February 10, 2012 updated by: Audis Bethea, Pharm.D., CAMC Health System

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All cause mortality
Time Frame: 28 days
All cause mortality during first 28-days after study randomization.
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Unable to define

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CAMC Health System

Investigators

  • Principal Investigator: John A Bethea, Pharm.D., Charleston Area Medical Center (CAMC)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

August 23, 2006

First Submitted That Met QC Criteria

August 23, 2006

First Posted (Estimate)

August 24, 2006

Study Record Updates

Last Update Posted (Estimate)

February 13, 2012

Last Update Submitted That Met QC Criteria

February 10, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-05-1813

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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