Efficacy of Hydrocortisone in Treatment of Severe Sepsis/Septic Shock Patients With Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)

Study Overview
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Brief Summary
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Severe sepsis/septic shock is a serious condition associated with high mortality rate. Hydrocortisone has been recommended as a useful treatment to decrease mortality in hemodynamically unstable septic shock patients, not response to fluid and moderate dose of vasopressor. During the progression of severe sepsis/septic shock, multi-organ dysfunction can develop. Acute lung injury (ALI) and its more severe form, acute respiratory syndrome (ARDS) is one of the common organ dysfunction associated with septic shock. Information from a meta-analysis suggested that moderate dose of hydrocortisone may improve the ARDS patients' outcome. Whether hydrocortisone can effectively prevent disease progression and death in severe sepsis/septic shock patients who complicated with ALI/ARDS has not been proven.

Detailed Description
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Severe sepsis/septic shock is a serious condition associated with high mortality rate. The pathophysiology of the disease involves the complex interaction between host's immunity and the microorganisms toxin. The release of immune complex and cascade of inflammatory cytokines are responsible for multiorgan dysfunction, especially the cardiovascular system. Hydrocortisone has been recommended as a useful treatment to decrease mortality in hemodynamically unstable septic shock patients, not response to fluid and moderate dose of vasopressor. Both anti-inflammation and supplementation of relatively adrenal insufficiency are the main hypothesis of the benefit of hydrocortisone. During the progression of severe sepsis/septic shock, multi-organ dysfunction can develop. Acute lung injury (ALI) and its more severe form, acute respiratory syndrome (ARDS) is one of the common organ dysfunction associated with septic shock. Although there is controversy about timing and favorable patients'characteristic, the information from a meta-analysis suggested that moderate dose of hydrocortisone may improve the ARDS patients' outcome. Whether hydrocortisone can effectively prevent disease progression and death in severe sepsis/septic shock patients who complicated with ALI/ARDS has not been proven.

Official Title
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Efficacy of Moderate Dose Hydrocortisone in Treatment of Severe Sepsis and Septic Shock Patients With Acute Lung Injury/Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

Conditions
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Septic Shock, Severe Sepsis, Acute Lung Injury, Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Placebo
* Drug: Hydrocortisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years and older Diagnosis of severe sepsis or septic shock according to the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference 1992 Diagnosis of acute lung injury or acute respiratory distress syndrome according to the American-European Consensus Conference on ARDS 1994 Onset of organ dysfunction within 12 hours before enrollment Exclusion Criteria: Indicated for receive corticosteroid Congestive heart failure Contra-indication for hydrocortisone: For example: allergy to hydrocortisone Pregnancy Not agree to sign the consent form

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Normal saline 50 ml intravenous every 6 hours for 7 days | Drug: Placebo<br>* Normal saline 50 ml intravenous every 6 hours for 7 days<br>|
| Active Comparator: Hydrocortisone<br>Hydrocortisone 50 mg intravenous every 6 hours for 7 days | Drug: Hydrocortisone<br>* Hydrocortisone 50 mg intravenous every 6 hours for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | Death from any cause at 28 days after diagnosis of severe sepsis/septic shock | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator free day | Day of alive within 28 days without mechanical ventilator support. | 28 day | 
| Vasopressor free day | Days of alive within 28 days without any doses of vasopressors including dopamine, norepinephrine, adrenaline or dobutamine. | 28 days | 
| Rate of renal replacement therapy | Proportion of the patients who received renal replacement therapy within 28 days after diagnosis of severe sepsis or septic shock. | 28 days | 
| Organ support free days | Days of alive without ventilator, renal replacement therapy and vasopressors within 28 days after diagnosis of severe sepsis or septic shock. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Septic shock, Severe sepsis, Acute lung injury, Acute respiratory distress syndrome, ARDS