Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome

• ClinicalTrials.gov Identifier: NCT00295269
• Recruitment Status: Completed
• First Posted: February 23, 2006
• Last Update Posted: May 9, 2006
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by: National Heart, Lung, and Blood Institute (NHLBI)

Study Description

Brief Summary:

The purpose of this study is to assess innovative treatment methods in patients with adult respiratory distress syndrome (ARDS) as well as those at risk of developing ARDS.

Condition or disease	Intervention/treatment	Phase
Acute Respiratory Distress Syndrome; Lung Diseases	Drug: Mythylprednisolone	Phase 3

Detailed Description:

BACKGROUND:

ARDS affects approximately 150,000 people in the United States each year. Despite twenty years of research into the mechanisms that cause this syndrome and numerous developments in the technology of mechanical ventilation, the mortality rate has remained greater than 50 percent. In addition to the tragic loss of human life, this condition poses a cost to society because these patients spend an average of two weeks in intensive care units and require multiple high tech procedures. Because of the overwhelming nature of the lung injury once it is established, prevention appears to be the most effective strategy for improving the outlook for those with ARDS.

Basic research has identified numerous inflammatory pathways that are associated with the development of ARDS. Agents that block these mediators prolong survival in animals with lung injury, and a few of them have been tested in human patients. Because of the large number of putative mediators and the variety of ways that their action can be blocked, the possibility for new drug development is almost infinite. This is an exciting prospect, since it envisions the first effective pharmacologic treatment for ARDS. However, preliminary clinical studies have shown conflicting results, and there is an urgent need for a mechanism to efficiently and effectively test new drugs in ARDS. Treatment studies in patients with ARDS are difficult to perform for three reasons. First, the complicated clinical picture makes it difficult to accumulate a large number of comparable patients in any one center. Secondly, there is no agreement on the optimal supportive care of these critically ill patients. Finally, many of the patients meeting study criteria will not be enrolled in study protocols because of the acute nature of the disease process. For these reasons, therapeutic trials in ARDS require multicenter cooperation.

DESIGN NARRATIVE:

This study compared the effect of corticosteroids with placebo in the management of late-phase (greater than seven days) ARDS. The study determined if the administration of the corticosteroid, methylprednisolone sodium succinate, in severe ARDS that was either stable or worsening after seven days, would reduce mortality and morbidity. The primary endpoint was mortality at 60 days. Secondary endpoints included ventilator-free days and organ failure-free days. LaSRS was designed to include 400 patients and began recruiting in the Spring of 1997. In October 1999, the data and safety monitoring board (DSMB) reduced the recruitment target number to 200 patients because the eligible patients were fewer than anticipated.

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: Late Steroid Rescue Study (LaSRS): The Efficacy of Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome
• Study Start Date: March 1997
• Study Completion Date: September 2005

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Mortality rates (measured at time of hospital discharge or 60 days after study entry)

Secondary Outcome Measures :

1. Number of ventilator-free days (measured at 28 days following study entry)
2. Number of organ failure-free days (measured at 28 days following study entry)
3. Reduction in markers of ongoing inflammation and fibroproliferation (measured at 7 days following study entry)

Eligibility Criteria

• Ages Eligible for Study: 13 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosed with ARDS or has risk factors for ARDS; individuals will be considered at risk if they are critically ill and have trauma, sepsis, shock, pneumonia, inhalation injury, drug overdose, pancreatitis, or hypertransfusion
• Onset of ARDS must be between 7 and 28 days prior to study entry
• Since ARDS onset, bilateral infiltrates must have persisted and participants must have required continuous mechanical ventilation

Contacts and Locations

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Edward Abraham; University of Colorado, Denver
• Principal Investigator: William Fulkerson; Duke University
• Principal Investigator: Leonard Hudson; University of Washington
• Principal Investigator: Paul Lanken; University of Pennsylvania
• Principal Investigator: Michael Matthay; University of California
• Principal Investigator: Alan Morris; Latter Day Saints Hospital
• Principal Investigator: David Schoenfeld; Massachusetts General Hospital
• Principal Investigator: Henry Silverman; University of Maryland, College Park
• Principal Investigator: Galen Toews; University of Michigan
• Principal Investigator: Arthur Wheeler; Vanderbilt University
• Principal Investigator: Herbert Wiedemann; The Cleveland Clinic

More Information

Additional Information:

Acute Respiratory Distress Syndrome Clinical Network [ARDSNet] 

Publications of Results:

Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006 Apr 20;354(16):1671-84.

• ClinicalTrials.gov Identifier: NCT00295269
• Other Study ID Numbers: 355; N01 HR46054; N01 HR46055; N01 HR46056; N01 HR46057; N01 HR46058; N01 HR46059; N01 HR46060; N01 HR46061; N01 HR46062; N01 HR46063; N01 HR46064
• First Posted: February 23, 2006
• Last Update Posted: May 9, 2006
• Last Verified: April 2006

Additional relevant MeSH terms:

Lung Diseases; Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome, Adult; Acute Lung Injury; Syndrome; Disease; Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury