Clinical trial NCT00295269: Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome
Official title: Late Steroid Rescue Study (LaSRS): The Efficacy of Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Respiratory Distress Syndrome
Lung Diseases
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 2006-02-23
Enrollment: 200
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Mortality rates (measured at time of hospital discharge or 60 days after study entry)
Secondary outcomes:
measure: Number of ventilator-free days (measured at 28 days following study entry)
measure: Number of organ failure-free days (measured at 28 days following study entry)
measure: Reduction in markers of ongoing inflammation and fibroproliferation (measured at 7 days following study entry)
Other outcomes:
Locations:
Study officials:
affiliation: University of Colorado, Denver
name: Edward Abraham
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: William Fulkerson
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Leonard Hudson
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Paul Lanken
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California
name: Michael Matthay
role: PRINCIPAL_INVESTIGATOR
affiliation: Latter Day Saints Hospital
name: Alan Morris
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: David Schoenfeld
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland
name: Henry Silverman
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Galen Toews
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University
name: Arthur Wheeler
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Herbert Wiedemann
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1056/NEJMoa051693.