Enrollment of 1,000 patients into the first ARDSNet protocol, "Ketoconazole and Respiratory Management in Acute Lung Injury/Acute Respiratory Distress Syndrome" (KARMA) began in the spring of 1996. KARMA assessed the efficacy of 6 ml/kg versus 12 ml/kg positive pressure ventilation in reducing mortality and morbidity in patients with acute lung injury and ARDS. It also assessed the efficacy of ketoconazole, a thromboxane synthetase inhibitor, in reducing mortality and morbidity in patients with acute lung injury and ARDS. The ketoconazole arm was stopped by the Data Monitoring Safety Board (DSMB) in January 1997 after the enrollment of 234 patients. Ketoconazole did not show any benefit in survival, duration of ventilation, or any measure of lung function. The ventilator arm of the protocol continued until March 10, 1999, and compared the efficacy of high (12 ml/kg) and low (6 ml/kg) tidal volume ventilation in reducing mortality and morbidity in patients with acute lung injury and ARDS. The ventilator portion of the trial was stopped on March 10, 1999, on the recommendation of the DSMB when the data from the first 861 patients showed approximately 25 percent fewer deaths among patients receiving small, rather than large, breaths of air from the mechanical ventilator.