Methods of using inhaled nitric oxide gas for treatment of acute respiratory distress syndrome in children
Inventors
Potenziano, Jim • Bronicki, Ronald • Baldassarre, James
Assignees
Mallinckrodt IP • Mallinckrodt Pharma IP Trading DAC • Mallinckrodt Pharmaceuticals Ireland Ltd • Therakos Inc • INO Therapeutics LLC
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Publication Number
US-10391120-B2
Publication Date
2019-08-27
Expiration Date
Abstract
The present invention provides a treatment of acute respiratory distress syndrome (ARDS) in children using dosing of nitric oxide at low concentrations, such as less than 10 ppm.
Core Innovation
The invention relates to a method of treating acute respiratory distress syndrome (ARDS) in children by administering a gas comprising nitric oxide (NO). The method provides administering NO gas at a dose in the range from about 2 ppm to about 8 ppm for a treatment period of at least 24 hours, and the child is determined to have an oxygenation index of greater than or equal to 12 cm H2O/mmHg.
The described pediatric treatment is supported by unexpected findings from a randomized, double-blind, placebo-controlled pediatric trial. The trial shows that inhaled nitric oxide (iNO) increases oxygenation index over time, improves days alive and ventilator-free at 28 days, and increases ECMO-free survival, while maintaining a comparable safety profile versus placebo.
The document describes eligibility criteria and administration context for mechanically ventilated children in pediatric intensive care unit (PICU). The treatment uses inhaled nitric oxide (iNO) at low concentrations within a range from less than 10 ppm, and includes an example of 5 ppm. The trial context includes assessing safety, including normal methemoglobin levels, and includes an iNO delivery system for mechanically ventilated children.
Claims Coverage
The independent claim covers treating acute respiratory distress syndrome (ARDS) in children by administering nitric oxide (NO) gas at a specified low-dose range for at least 24 hours, conditioned on an oxygenation index threshold. Dependent claims further refine patient selection and treatment parameters, including additional oxygenation criteria, radiographic findings, demographic constraints, treatment duration limits, and exclusion of extracorporeal membrane oxygenation during NO administration.
Treating pediatric ards with low-dose nitric oxide gas for oxygenation-index-selected children
Administering a gas comprising nitric oxide (NO) to a child in need thereof at a dose in the range from about 2 ppm to about 8 ppm NO for a treatment period of at least 24 hours, wherein the child is determined to have an oxygenation index of greater than or equal to 12 cm H2O/mmHg.
Oxygenation-index selection using PaO2/FiO2 ratio
The method includes determining that a child has a PaO2/FiO2 ratio of less than 300 based on partial pressure of oxygen in arterial blood and fraction of inspired oxygen.
Narrowing the NO dose range to 2–6 ppm
The method includes administering NO at a dose ranging from about 2 ppm to about 6 ppm.
Limiting treatment duration
The method is performed by administering NO for a treatment period up to 2 months.
Excluding extracorporeal membrane oxygenation during NO administration
The method is performed without subjecting the child to extracorporeal membrane oxygenation during NO administration.
Radiographic and timing-limited eligibility using unilateral infiltrates on chest x-ray
The method is further limited to children whose chest x-ray shows at least unilateral infiltrates, with the x-ray taken within 24 hours of starting treatment.
Across the independent claim and its refinements, the core inventive coverage is low-dose NO gas administration for at least 24 hours to children with oxygenation-index-defined ARDS, with dependent claim features further specifying oxygenation selection criteria, narrowing the NO dose range, limiting treatment duration, excluding extracorporeal membrane oxygenation during NO administration, and requiring unilateral infiltrates on a chest x-ray obtained within 24 hours of starting treatment.
Stated Advantages
Increases oxygenation index over time.
Improves days alive and ventilator-free at 28 days.
Increases ECMO-free survival.
Comparable safety profile versus placebo, including normal methemoglobin levels.
Documented Applications
Treating acute respiratory distress syndrome (ARDS) in children by administering inhaled nitric oxide (iNO) at low concentrations to mechanically ventilated children in pediatric intensive care unit (PICU), supported by randomized, double-blind, placebo-controlled pediatric trial outcomes.
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