Ketoconazole for ALI/ARDS: The first clinical trial completed by the Network was a randomized, controlled trial of Ketoconazole versus placebo in patients with acute lung injury and ARDS. Ketoconazole was chosen because of its anti-inflammatory actions noted in the laboratory and because previous Phase II 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 ineffective. The clinical trial results were published in JAMA in April 2000 (The ARDS Clinical Trials Network Authors for the ARDS Network. Ketoconazole for early treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome. A randomized controlled trial. JAMA, 2000;283:1995-2002).
Lysophylline for ALI/ARDS: A second randomized placebo controlled trial compared Lisofylline, an antiinflammatory and antioxidant drug that also showed promising results in phase II trials of immunosuppressed patients. Lisofylline also proved to be ineffective and these clinical trial results were published in the journal Critical Care Medicine (The ARDS clinical Trials Network. Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome. Crit Care Med Vol 30:1-6).
Lower Tidal Volume Trial: A third trial examined lower tidal volume ventilation versus a traditionally recommended higher tidal volume approach in patients with acute lung injury. This landmark randomized controlled trial, which enrolled 861 subjects, clearly demonstrated that lower tidal volumes result in improved survival, with a similar need for sedatives for patient comfort. This study was published in the New England Journal of Medicine (The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; Vol 342: 1301-1308) If the results are applied to the care of patients across the country, tens of thousands of deaths per year will be prevented.
ALVEOLI: A fourth trial examined the role of higher positive end-expiratory pressure (PEEP) to keep the lung open between breaths and to further improve lung healing and repair during acute lung injury. The ALVEOLI study tested lower tidal volumes with with higher PEEP and, after enrolling 449 patients, found no further improvement in survival with the addition of higher PEEP. (Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher vs. lower positive end-expiration pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004 Jul 22;351(4):327-36).
Late Steroid rescue Study: LaSRS: The use of corticosteroids in the later phases of ARDS showed promise in a small randomized controlled trial. The ARDS Network enrolled 200 patients over 6 years in a placebo controlled trial of methylprednisolone versus placebo for patients with presistend ARDS after 7 to 28 days. Methyplrednisolone improved lung function resulting in earlier liberation from mechanical ventilation. Unfortunately, these promising findings did not result in improved survival. The findings were published in the New England Journal of Medicine in 2007. (The 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;354:1671-168)
FACTT: This study examined two different strategies for managing intravenous fluids and fluid balance in patients with acute lung injury. A second goal of this trial was to determine if a Pulmonary Artery Catheter (PAC) was superior to a smaller, and less invasive central venous catheter in the management of patients with ARDS. This trial answered these two important questions in a single trial. No benefit was seen with the PAC guided therapy and the strategy of restrictive or conservative fluid administration was superior to the traditional approach by shortening the duration of mechanical ventilation.