Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2).

Chong Lei; Binxiao Su; Hailong Dong; Andrea Bellavia; Raffaele Di Fenza; Bijan Safaee Fakhr; Stefano Gianni; Luigi Giuseppe Grassi; Robert Kacmarek; Caio Cesar Araujo Morais; Riccardo Pinciroli; Emanuele Vassena; Lorenzo Berra

Harms. Organ failure, prolonged hospitalization and mortality will be recorded as part of the study defined outcomes. Other adverse events will be monitored by the site PI and research specialist in real time from the start of randomization to hospital discharge or death. Reportable adverse events will include hemodynamic change and deterioration of oxygenation related to NO inhalation and require the adjustment of NO concentration. A serious adverse event in this study will be defined as a reportable adverse event that is fatal, life-threatening, or permanently disabling. All adverse events will be indicated on the data forms for the study and on the specific adverse event report forms and all serious adverse events will be reported to the site IRB within 48 hours of the research team learning about the event followed by more detailed written report to the local IRB. The following information about adverse events will be collected: 1) the onset and resolution of the event, 2) an assessment of the severity or intensity of the event, 3) an assessment of the relationship of the event to the intervention, and 4) any action taken because of event. Sites will inform the principle investigators (CL and LB) at the coordinating centers (Xijing Hospital and Massachusetts General Hospital) for any related adverse events directly caused by inhalation of NO (non-serious) within 14 days of discovery. All fatal, life-threatening, or permanently disabling (regardless of relatedness) events due to inhalation of NO must be reported to the coordinating centers within 48 hours of discovery. The principle investigators will report these events to the DSMB and to the coordinating centers IRBs.