Methods of reducing the risk of occurrence of pulmonary edema in children in need of treatment with inhaled nitric oxide

• US 8,282,966 B2
• Filed: 06/22/2010
• Issued: 10/09/2012
• Est. Priority Date: 06/30/2009
• Status: Active Grant

• Current Assignee: Mallinckrodt Critical Care Finance Inc (Mallinckrodt plc), Mallinckrodt Pharma Ip Trading DAC (Mallinckrodt plc), Therakos, Inc (Mallinckrodt plc)
• Original Assignee: INO Therapeutics LLC (Mallinckrodt plc)
• Inventors: Baldassarre, James S., Rosskamp, Ralf
• Primary Examiner(s): Arnold, Ernst
• Application Number:
  US12/821,020
• Publication Number:
  US 20100330207A1
• Time in Patent Office: 840 Days
• Field of Search: None
• US Class Current: 424/718
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/0205 Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
• CPC Class Codes: A61B 5/08 Detecting, measuring or recording devices for evaluating the respiratory organs A61B5/0205 takes precedence
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: A61B 5/7278 Artificial waveform generation or derivation, e.g. synthesising signals from measured signals A61B5/327 takes precedence
• CPC Class Codes: A61B 8/0883 for diagnosis of the heart
• CPC Class Codes: A61B 8/48 Diagnostic techniques A61B8/13 takes precedence
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/04 Nitro compounds
• CPC Class Codes: A61K 31/21 Esters, e.g. nitroglycerine, selenocyanates
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61M 16/0057 Pumps therefor
• CPC Class Codes: A61M 16/104 specially adapted for anaesthetics A61M16/18 takes precedence
• CPC Class Codes: A61M 16/12 by mixing different gases
• CPC Class Codes: A61M 60/139 inside the aorta, e.g. intra-aortic balloon pumps
• CPC Class Codes: A61M 60/295 Balloon pumps for circulatory assistance
• CPC Class Codes: A61M 60/497 for balloon pumps for circulatory assistance
• CPC Class Codes: A61M 60/841 of balloon pumps for circulatory assistance
• CPC Class Codes: A61M 60/857 : Implantable blood tubes
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: F17C 2201/058 : portable (<30 l)
• CPC Class Codes: F17C 2203/0646 : Aluminium
• CPC Class Codes: F17C 2221/014 : Nitrogen
• CPC Class Codes: F17C 2221/03 : Mixtures
• CPC Class Codes: F17C 2223/0123 : gaseous, e.g. CNG, GNC
• CPC Class Codes: F17C 2223/036 : Very high pressure (>80 bar)
• CPC Class Codes: F17C 2270/025 : Breathing
• CPC Class Codes: G06Q 99/00 : Subject matter not provided for in other groups of this subclass
• CPC Class Codes: G16H 20/10 : relating to drugs or medications, e.g. for ensuring correct administration to patients

Abstract

The invention relates methods of reducing the risk or preventing the occurrence of an adverse event (AE) or a serious adverse event (SAE) associated with a medical treatment comprising inhalation of nitric oxide.

Claims

1. A method of reducing the risk of occurrence of pulmonary edema associated with a medical treatment comprising inhalation of 20 ppm nitric oxide gas, said method comprising:

(a) performing echocardiography to identify a child in need of 20 ppm inhaled nitric oxide treatment for pulmonary hypertension, wherein the child is not dependent on right-to-left shunting of blood;

(b) determining that the child identified in (a) has a pulmonary capillary wedge pressure greater than or equal to 20 mm Hg and thus has left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide; and

(c) excluding the child from inhaled nitric oxide treatment based on the determination that the child has left ventricular dysfunction and so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.

2. The method of claim 1, wherein the child is a neonate.

3. The method of claim 1, wherein step (b) comprises measuring the child'"'"'s pulmonary capillary wedge pressure.

4. The method of claim 1, wherein the child'"'"'s left ventricular dysfunction is attributable to congenital heart disease.

5. The method of claim 1, wherein the child is determined to be at particular risk not only of pulmonary edema, but also of other Serious Adverse Events, upon treatment with inhaled nitric oxide, and the child is excluded from inhaled nitric oxide treatment based on the determination that the child has left ventricular dysfunction and so is at particular risk not only of pulmonary edema, but also of other Serious Adverse Events, upon treatment with inhaled nitric oxide.

6. A method of reducing the risk of occurrence of pulmonary edema associated with a medical treatment comprising inhalation of 20 ppm nitric oxide gas, said method comprising:

(a) carrying out a diagnostic process comprising measuring blood oxygen level, to identify a child as being in need of 20 ppm inhaled nitric oxide treatment for hypoxic respiratory failure, wherein the child is not dependent on right-to-left shunting of blood;

(b) determine determining that the child has a pulmonary capillary wedge pressure greater than or equal to 20 mm Hg and thus has left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide; and

(c) excluding the child from treatment with inhaled nitric oxide based on the determination that the child has left ventricular dysfunction and so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.

7. The method of claim 6, wherein the diagnostic process of step (a) further comprises performing echocardiography.

8. The method of claim 6, wherein the child is a neonate.

9. The method of claim 6, wherein step (b) comprises measuring the child'"'"'s pulmonary capillary wedge pressure.

10. The method of claim 6, wherein the left ventricular dysfunction is attributable to congenital heart disease.

11. The method of claim 6, wherein the child is determined to be at particular risk not only of pulmonary edema, but also of other Serious Adverse Events, upon treatment with inhaled nitric oxide, and the child is excluded from inhaled nitric oxide treatment based on the determination that the child has left ventricular dysfunction and so is at particular risk not only of pulmonary edema, but also other Serious Adverse Events, upon treatment with inhaled nitric oxide.

12. The method of claim 11, wherein the left ventricular dysfunction is attributable to congenital heart disease.

13. A method of treatment comprising:

(a) performing echocardiography to identify a plurality of children who are in need of 20 ppm inhaled nitric oxide treatment for pulmonary hypertension, wherein the children are not dependent on right-to-left shunting of blood;

(b) determining that a first child of the plurality has a pulmonary capillary wedge pressure greater than or equal to 20 mm Hg and thus has left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide;

(c) determining that a second child of the plurality does not have left ventricular dysfunction;

(d) administering the 20 ppm inhaled nitric oxide treatment to the second child; and

(e) excluding the first child from treatment with inhaled nitric oxide, based on the determination that the first child has left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.

14. The method of claim 13, wherein step (a) further comprises measuring blood oxygen levels in the first and second children and thereby determining that the first and second children are hypoxic.

15. The method of claim 13, wherein the second child has congenital heart disease.

16. The method of claim 13, wherein step (b) comprises measuring the first child'"'"'s pulmonary capillary wedge pressure.

17. The method of claim 13, wherein determining that the second child of the plurality does not have pre-existing left ventricular dysfunction comprises performing echocardiography.

18. The method of claim 13, wherein the left ventricular dysfunction is attributable to congenital heart disease.

19. The method of claim 13, wherein the left ventricular dysfunction of the first child is attributable to congenital heart disease.

20. The method of claim 13, wherein the first child is determined to be at particular risk not only of pulmonary edema, but also of other Serious Adverse Events, upon treatment with inhaled nitric oxide, and the first child is excluded from inhaled nitric oxide treatment based on the determination that the first child has left ventricular dysfunction and so is at particular risk not only of pulmonary edema, but also other Serious Adverse Events, upon treatment with inhaled nitric oxide.

21. The method of claim 20, wherein the pre-existing left ventricular dysfunction of the first child is attributable to congenital heart disease.

22. A method of treatment comprising:

(a) identifying a plurality of children who are in need of 20 ppm inhaled nitric oxide treatment, wherein the children are not dependent on right-to-left shunting of blood;

(b) in the first child of the plurality, measuring pulmonary capillary wedge pressure to determine that the first child of the plurality has a pulmonary capillary wedge pressure greater than or equal to 20 mm Hg and thus has left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide;

(c) in the second child of the plurality, performing echocardiography and/or measurement of pulmonary capillary wedge pressure to determine that the second child of the plurality does not have left ventricular dysfunction;

(d) administering the 20 ppm inhaled nitric oxide treatment to the second child; and

(e) excluding the first child from treatment with inhaled nitric oxide, based on the determination that the first child has left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.

23. The method of claim 22, wherein step (a) comprises performing echocardiography to determine that the first and second children have pulmonary hypertension.

24. The method of claim 22, wherein step (a) comprises measuring blood oxygen levels in the first and second children and thereby determining that the first and second children are hypoxic.

25. The method of claim 22, wherein the second child has congenital heart disease.

26. The method of claim 22, wherein the left ventricular dysfunction is attributable to congenital heart disease.

27. The method of claim 22, wherein the pre-existing left ventricular dysfunction of the first child is attributable to congenital heart disease.

28. The method of claim 22, wherein the first child is determined to be at particular risk not only of pulmonary edema, but also of other Serious Adverse Events, upon treatment with inhaled nitric oxide, and the first child is excluded from inhaled nitric oxide treatment based on the determination that the first child has pre-existing left ventricular dysfunction and so is at particular risk not only of pulmonary edema, but also other Serious Adverse Events, upon treatment with inhaled nitric oxide.

29. The method of claim 28, wherein the pre-existing left ventricular dysfunction of the first child is attributable to congenital heart disease.