Abstract
Background
Acute respiratory distress syndrome (ARDS) is caused by rapid onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of ARDS patients, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS.Methods
The Therapeutic Iloprost during ARDS ( ThIIo-Trial) is a multicenter, randomized, clinical phase II trial assessing the efficacy of inhaled Iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index, a health care-related questionnaire and frailty (Vulnerable Elderly Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO 2 /FiO 2 . Secondary endpoints include 90-day all-cause mortality, SOFA scores during the study period up to day 90, the duration of mechanical ventilation, the length of ICU stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness and discharge localization. The study will be conducted in three university ARDS centers in Germany.Discussion
The results of the ThIlo-Trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in ARDS patients.