Article ID Journal Published Year Pages File Type
2613880 Réanimation 2007 5 Pages PDF
Abstract
There is no pathophysiological medicinal treatment of Acute Respiratory Disease Syndrome (ARDS). In light of the failure of previous therapeutic trials, three questions should be asked before considering a therapeutic trial in ARDS: why (the pathophysiological target, it is often detailed), when (the optimal therapeutic window) and which end-point (the rational of the calculation of the sample size). This latter question is of major importance, since some valuable therapeutics will be abandoned due to a too ambitious mortality end-point. The recent validation of biomarkers of prognostic value in ARDS by the “biological” studies derived from the ARDS Clinical Trials Network should constitute more conformed end-points to phase II trials, which is an indispensable prerequisite for phase III trials with justified calculation of sample size. Three “inadequate” biological processes could constitute interesting pathophysiological targets: 1) the decompartmentalization of the inflammatory response with involvement of the whole lung and systemic spill over, 2) the occurrence of alveolar inflammation in absence of pathophysiological reason/necessity (ARDS due to non pulmonary causes for instance), and 3) the perpetuation or repetition of lung injury while the initial process (pneumonia for instance) seems controlled, as if the resolution of the inflammatory response could not occur.
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