Inhaled nitric oxide to treat intermediate risk pulmonary embolism

A multicenter randomized controlled trial

Jeffrey Kline, Michael A. Puskarich, Alan E. Jones, Ronald Mastouri, Cassandra L. Hall, Anthony Perkins, Emily E. Gundert, Tim Lahm

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)60-68
Number of pages9
JournalNitric Oxide - Biology and Chemistry
Volume84
DOIs
StatePublished - Mar 1 2019

Fingerprint

Echocardiography
Pulmonary Embolism
Nitric Oxide
Randomized Controlled Trials
Oxygen
Troponin T
Troponin
Brain Natriuretic Peptide
Blood
Nitrogen
Plasmas
Placebos
Composite materials
Dilatation
Dyspnea
Sample Size
Hypotension
Clinical Trials

Keywords

  • Brain natriuretic peptide
  • Echocardiography
  • Heart failure
  • Nitric oxide
  • Pulmonary embolism
  • Pulmonary hypertension
  • Randomized trial
  • Troponin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Cite this

Inhaled nitric oxide to treat intermediate risk pulmonary embolism : A multicenter randomized controlled trial. / Kline, Jeffrey; Puskarich, Michael A.; Jones, Alan E.; Mastouri, Ronald; Hall, Cassandra L.; Perkins, Anthony; Gundert, Emily E.; Lahm, Tim.

In: Nitric Oxide - Biology and Chemistry, Vol. 84, 01.03.2019, p. 60-68.

Research output: Contribution to journalArticle

Kline, Jeffrey ; Puskarich, Michael A. ; Jones, Alan E. ; Mastouri, Ronald ; Hall, Cassandra L. ; Perkins, Anthony ; Gundert, Emily E. ; Lahm, Tim. / Inhaled nitric oxide to treat intermediate risk pulmonary embolism : A multicenter randomized controlled trial. In: Nitric Oxide - Biology and Chemistry. 2019 ; Vol. 84. pp. 60-68.
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AU - Jones, Alan E.

AU - Mastouri, Ronald

AU - Hall, Cassandra L.

AU - Perkins, Anthony

AU - Gundert, Emily E.

AU - Lahm, Tim

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AB - 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.

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