Persistent Pulmonary Hypertension of the Newborn

Inclusion Criteria:

1. Signed informed consent by the parent(s) or the legal representative(s).

2. Term and near term newborns (gestational age > 34 weeks).

3. Post natal age ≥ 12 hours and < 7 days.

4. Weight at birth ≥ 2,500 g.

5. Idiopathic PPHN or PPHN due to parenchymal lung disease

6. Pulmonary hypertension (PH) confirmed by echocardiography:

7. Need for continued iNO at a dose > 10ppm after at least 4 hours of continuous iNO
treatment.

8. Two oxygenation index (OI) values ≥ 15 taken at least 30 minutes apart, in the 12
hours prior to randomization and while the patient is receiving iNO treatment.

9. Mechanical ventilation with fraction of inspired oxygen (FiO2) ≥ 50%.

Exclusion Criteria:

1. PH associated with conditions other than PPHN.

2. Immediate need for cardiac resuscitation or extracorporeal membrane oxygenation
(ECMO) (profound hypoxemia [PaO2] < 30 mm Hg; OI > 40).

3. Lethal congenital anomalies.

4. Congenital Diaphragmatic Hernia.

5. Significant congenital heart disease or significant left to right shunt.

6. Medically significant pneumothorax.

7. Active seizures.

8. Expected duration of mechanical ventilation of less than 48 hours.

9. Mean systemic blood pressure < 35 mmHg despite therapy with volume infusions and
cardiotonic support.

10. Hepatic failure or all conditions with either AST or ALT values > 2 x ULN.

11. Renal function impairment such as serum creatinine > 3 x ULN or anuria.

12. Known intracranial hemorrhage grade III or IV.

13. Either hemoglobin or hematocrit level < 75% of the LLN.

14. Thrombocytopenia (platelet count < 50,000 cells /µL).

15. Leukopenia (WBC < 2,500 cells/ µL).

16. Any condition precluding the use of a nasogastric/orogastric tube.

17. Administration of prohibited medication prior to randomization.