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.
Bibliographical noteFunding Information:
The trial was sponsored by the National Institutes of Health ( UM1HL113203-01 ) and by an investigator initiated grant from Mallinckrodt Pharmaceuticals and Roche Diagnostics in 2015. The sponsors had no role in the protocol design, data analysis or manuscript writing.
© 2019 Elsevier Inc.
- Brain natriuretic peptide
- Heart failure
- Nitric oxide
- Pulmonary embolism
- Pulmonary hypertension
- Randomized trial
- Double-Blind Method
- Middle Aged
- Administration, Inhalation
- Ventricular Dysfunction, Right/drug therapy
- Pulmonary Embolism/drug therapy
- Troponin T/metabolism
- Nitric Oxide/administration & dosage
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Randomized Controlled Trial
- Multicenter Study
- Journal Article
- Research Support, N.I.H., Extramural