Elsevier

Critical Care Clinics

Volume 27, Issue 3, July 2011, Pages 459-468
Critical Care Clinics

ARDS Network (NHLBI) Studies: Successes and Challenges in ARDS Clinical Research

https://doi.org/10.1016/j.ccc.2011.05.011Get rights and content

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History and goal of the ARDS Network

To hasten the development of effective therapy for acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, initiated a clinical network to carry out multicenter clinical trials of ARDS treatments. The ARDS Network was established as a contract program in 1994 following a national competition.

The ARDS Network is a clinical research network of approximately 42 hospitals, organized into 12 clinical sites, and a Clinical

Ketoconazole for ALI/ARDS

Study status: Completed.

Study dates: March 1996 to February 1998.

The first clinical trial completed by the Network was a randomized, controlled trial of ketoconazole versus placebo in patients with ALI and ARDS. Ketoconazole was chosen because of its anti-inflammatory actions noted in the laboratory and because previous phase 2 clinical trials suggested benefit in patients with or at risk for ARDS. This trial was stopped early by the DSMB in January 1997 after finding ketoconazole to be

Lower tidal volume trial

Study status: Completed.

Study dates: March 1996 to July 1999.

This landmark third trial examined lower tidal volume ventilation versus a traditionally recommended larger tidal volume approach in patients with ALI. This trial was undertaken because extensive animal studies and 2 small clinical trials suggested lung stretch with larger tidal volumes may injure the lung or prevent recovery. However, 2 other clinical trials raised questions about this hypothesis, and the use of smaller tidal volumes

Late steroid rescue study: LaSRS

Study status: Completed.

Study dates: August 1997 to November 2003.

The late phase of ARDS is often characterized by excessive fibroproliferation leading to gas exchange and compliance abnormalities. Although corticosteroids are not effective in early ARDS, several case reports and uncontrolled case series and one small randomized, controlled trial suggest that corticosteroids may be useful in the management of late-phase ARDS. To test this hypothesis a randomized, double-blinded trial comparing

Lysofylline for ALI/ARDS

Study status: Completed.

Study dates: February 1998 to June 1999.

The LARMA study was a randomized, double-blind, placebo-controlled multicenter 2 × 2 factorial study wherein each patient was randomized between lisofylline and placebo. It was designed to test whether the administration of lisofylline early after the onset of ALI or ARDS would reduce mortality and morbidity. The study was stopped by the DSMB for futility at the first scheduled interim analysis. The decision was based on

ALVEOLI study

Study status: Completed.

Study dates: November 1999 to March 2002.

Prospective, Randomized, Multi-Center Trial of Higher End-Expiratory Lung Volume/Lower FiO2 versus Lower End-expiratory Lung Volume/Higher FiO2 Ventilation in Acute Lung Injury and Acute Respiratory Distress Syndrome.

This study was a prospective, randomized, controlled multicenter trial. The objective was to compare clinical outcomes of patients with ALI and ARDS treated with a higher end-expiratory lung volume/lower FiO2 versus a

Fluid and catheter treatment trial: FACTT

Study status: Completed.

Study dates: June 2000 to October 2005.

Prospective, Randomized, Multi-Center Trial of Pulmonary Artery Catheter (PAC) versus Central Venous Catheter (CVC) for Management of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) and Prospective, Randomized, Multi-Center Trial of “Fluid Conservative” versus “Fluid Liberal” Management of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).

This study examined two different strategies for

Albuterol for the treatment of ALI: ALTA

Study status: Closed.

Study dates: August 2007 to September 2008.

ALTA was a prospective, randomized trial of aerosolized albuterol versus placebo to test the safety and efficacy of aerosolized β2-adrenergic agonist therapy for improving clinical outcomes in patients with ALI. Aerosolized β2-agonist therapy was anticipated to diminish the formation of lung edema, enhance clearance of lung edema, and decrease pulmonary inflammation in patients with ALI. Because β2-agonists have been shown to

EDEN-Omega study

Study status: Open.

Study dates: November 2006.

Prospective, Randomized Trial of Initial Trophic Enteral Feeding Followed by Advancement to Full-Calorie Enteral Feeding Versus Early Advancement to Full-Calorie Enteral Feeding (http://clinicaltrials.gov/ct2/show/NCT00609180).

This trial ran simultaneously with a trial of omega-3 fatty acid, γ-linolenic acid, and antioxidant supplementation versus a comparator. The ARDSNet trial used an omega-3 and antioxidant supplement added to “usual” feeding

Statins for acutely injured lungs from sepsis: SAILS

Study status: Open.

Study dates: March 2010.

The SAILS study is a trial of rosuvastatin versus placebo comparator for the treatment of patients with ALI or ARDS. The objective is to assess the efficacy and safety of oral rosuvastatin in patients with sepsis-induced ALI. The hypothesis of this study is that pleiotropic anti-inflammatory effects of rosuvastatin therapy will improve mortality in patients with sepsis-induced ALI.

This study is a prospective, randomized, controlled multicenter trial.

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