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

Sponsor

Mahidol University (Other)

Overall Status

Completed

CT.gov ID

NCT01284452

Collaborator

(none)

197

Enrollment

Location

Arms

Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Septic Shock Severe Sepsis Acute Lung Injury Acute Respiratory Distress Syndrome	Drug: Placebo Drug: Hydrocortisone	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

197 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Normal saline 50 ml intravenous every 6 hours for 7 days	Drug: Placebo Normal saline 50 ml intravenous every 6 hours for 7 days
Active Comparator: Hydrocortisone Hydrocortisone 50 mg intravenous every 6 hours for 7 days	Drug: Hydrocortisone Hydrocortisone 50 mg intravenous every 6 hours for 7 days

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Normal saline 50 ml intravenous every 6 hours for 7 days

Drug: Placebo

Normal saline 50 ml intravenous every 6 hours for 7 days

Active Comparator: Hydrocortisone

Hydrocortisone 50 mg intravenous every 6 hours for 7 days

Drug: Hydrocortisone

Hydrocortisone 50 mg intravenous every 6 hours for 7 days

Outcome Measures

Primary Outcome Measures

All cause mortality [28 days]
Death from any cause at 28 days after diagnosis of severe sepsis/septic shock

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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