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

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

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Acute Respiratory Distress Syndrome; Acute Lung Injury; Severe Sepsis
• Intervention / Treatment: Drug: Placebo; Drug: Hydrocortisone

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 Type: Interventional
• Enrollment (Actual): 197
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Principal Investigator: Surat Tongyoo, MD, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University

Publications and helpful links

General Publications

• Tongyoo S, Permpikul C, Mongkolpun W, Vattanavanit V, Udompanturak S, Kocak M, Meduri GU. Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled trial. Crit Care. 2016 Oct 15;20(1):329. doi: 10.1186/s13054-016-1511-2.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: January 18, 2011
• First Submitted That Met QC Criteria: January 26, 2011
• First Posted (Estimate): January 27, 2011

Study Record Updates

• Last Update Posted (Estimate): April 20, 2015
• Last Update Submitted That Met QC Criteria: April 17, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Septic shock; ARDS; Acute respiratory distress syndrome; Severe sepsis; Acute lung injury
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Sepsis; Toxemia; Syndrome; Shock, Septic; Wounds and Injuries; Shock; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: Si630/2010