Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism

The iNOPE trial

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The study hypothesis is that administration of inhaled nitric oxide (NO) plus oxygen to subjects with submassive pulmonary embolism (PE) will improve right ventricular (RV) systolic function and reduce RV strain and necrosis, while improving patient dyspnea, more than treatment with oxygen alone. Methods This article describes the rationale and protocol for a registered (NCT01939301), nearly completed phase II, 3-center, randomized, double-blind, controlled trial. Eligible patients have pulmonary imaging–proven acute PE. Subjects must be normotensive, and have RV dysfunction on echocardiography or elevated troponin or brain natriuretic peptide and no fibrinolytics. Subjects receive NO plus oxygen or placebo for 24 hours (±3 hours) with blood sampling before and after treatment, and mandatory echocardiography and high-sensitivity troponin posttreatment to assess the composite primary end point. The sample size of N = 78 was predicated on 30% more NO-treated patients having a normal high-sensitivity troponin (<14 pg/mL) and a normal RV on echocardiography at 24 hours with α = .05 and β = .20. Safety was ensured by continuous spectrophotometric monitoring of percentage of methemoglobinemia and a predefined protocol to respond to emergent changes in condition. Blinding was ensured by identical tanks, software, and physical shielding of the device display and query of the clinical care team to assess blinding efficacy. Results We have enrolled 78 patients over a 31-month period. No patient has been withdrawn as a result of a safety concern, and no patient has had a serious adverse event related to NO. Conclusions We present methods and a protocol for the first double-blinded, randomized trial of inhaled NO to treat PE.

Original languageEnglish (US)
Pages (from-to)100-110
Number of pages11
JournalAmerican Heart Journal
Volume186
DOIs
StatePublished - Apr 1 2017

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Pulmonary Embolism
Nitric Oxide
Troponin
Echocardiography
Oxygen
Right Ventricular Dysfunction
Methemoglobinemia
Safety
Right Ventricular Function
Brain Natriuretic Peptide
Dyspnea
Sample Size
Necrosis
Software
Placebos
Equipment and Supplies
Lung
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism : The iNOPE trial. / Kline, Jeffrey; Hall, Cassandra L.; Jones, Alan E.; Puskarich, Michael A.; Mastouri, Ronald; Lahm, Tim.

In: American Heart Journal, Vol. 186, 01.04.2017, p. 100-110.

Research output: Contribution to journalArticle

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