Kline, Jeffrey A.Puskarich, Michael A.Jones, Alan E.Mastouri, Ronald A.Hall, Cassandra L.Perkins, AnthonyGundert, EmilyLahm, Tim2019-02-072019-02-072019-03Kline, J. A., Puskarich, M. A., Jones, A. E., Mastouri, R. A., Hall, C. L., Perkins, A., … Lahm, T. (2019). Inhaled nitric oxide to treat intermediate risk pulmonary embolism: A multicenter randomized controlled trial. Nitric Oxide, 84, pp. 60-68. https://doi.org/10.1016/j.niox.2019.01.006https://hdl.handle.net/1805/18325Objective 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 h. 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 h, 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 h (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.enPublisher Policynitric oxiderandomized trialpulmonary embolismArticle