2.3. Intervention:

All patients with PE were randomized to either NO (50 ppm) or nitrogen plus oxygen delivered via a commercially available, FDA cleared device (INOvent; Mallinckrodt Pharmaceauticals; Clinton, NJ) equipped with a shield that blinded investigators to study group assignment. As described in detail in a methods publication, the dose of 50 ppm by nasal cannula was based upon results from case reports and the authors’ experience from a phase I study.(Kline et al., 2017; Kline et al., 2014) Patients received 24 hours of continuous treatment and were followed for clinical study outcomes. All patient assessments and study measurements were performed by study staff and investigators blinded to the treatment allocation.

Blood was drawn by qualified phlebotomists following a waste using 18 gauge needles into two (blue-top) tubes containing sodium citrate and 3 tubes containing K₂EDTA at two time points; prior to initiation of treatment or placebo, and just prior to initiation of study drug weaning (24 ± 2 hours following initiation). Blood was transported at room temperature (~23 °C) and processed within 60 minutes.