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

ABSTRACT: 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?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. CLINICAL TRIAL REGISTRATION:NCT01939301.

SUBMITTER: Kline JA 

PROVIDER: S-EPMC7047892 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature