Inhaled nitric oxide to treat intermediate risk pulmonary embolism: A multicenter randomized controlled trial

Objective: To test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE. Methods: This was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had RV dysfunction and a treatment plan of standard anticoagulation. Subjects received either oxygen plus 50 parts per million nitrogen (placebo) or oxygen plus 50 ppm NO for 24 hours. The primary composite endpoint required a normal RV on echocardiography and a plasma troponin T concentration <14 pg/mL. The secondary endpoint required a blood brain natriuretic peptide concentration < 90 pg/mL and a Borg dyspnea score <=2. The sample size of N=76 tested if 30% more patients treated with NO would achieve the primary endpoint with 80% power and alpha=5%. Results: We randomized 78 patients and after two withdrawals, 38 were treated per protocol in each group. Patients were well matched for baseline conditions. At 24 hours, 5/38 (13%) of patients treated with placebo and 9/38 (24%) of patients treated with NO reached the primary endpoint (P=0.375). The secondary endpoint was reached in 34% with placebo and 13% of the NO (P=0.11). In a pre-planned post-hoc analysis, we examined how many patients with RV hypokinesis or dilation at enrollment resolved these abnormalities; 29% more patients treated with NO resolved both abnormalities at 24 hours (P=0.010, Cochrane’s Q test). Conclusions: In patients with severe submassive PE, inhaled nitric oxide failed to increase the proportion of patients with a normal troponin and echocardiogram but increased the probability of eliminating RV hypokinesis and dilation on echocardiography.