Persistent Pulmonary Hypertension of the Newborn
Condition: Persistent Pulmonary Hypertension of the Newborn
MeSH terms: Hypertension, Pulmonary; Persistent Fetal Circulation Syndrome; Hypertension
Intervention: Bosentan; Matching placebo
Intervention description: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.; twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.
Intervention MeSH terms: Bosentan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 23.0
Sex: All
Minimum age: 12 Hours
Maximum age: 7 Days
Healthy volunteers: No
Keywords: Persistent pulmonary hypertension, newborn; PPHN

Summary:

      The AC-052-391-study is a phase 3 study to investigate whether adding bosentan to inhaled
      nitric oxide in newborns with persistent pulmonary hypertension of newborns (PPHN) is a
      supporting and safe therapy and to evaluate the pharmacokinetics of bosentan and its
      metabolites.
    

Eligibility criteria:

        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 ≥ 2,000 g.

          5. Idiopathic PPHN or PPHN due to parenchymal lung disease

          6. Documented diagnosis of pulmonary hypertension (PH) confirmed by echocardiography.

          7. Need for continued inhaled nitric oxide (iNO) at a dose > 10ppm after at least 4 hours
             of continuous iNO treatment.

          8. Two oxygenation index (OI) values ≥ 12 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% at randomization.

        Exclusion Criteria:

          1. PH associated with conditions other than PPHN.

          2. Immediate need for cardiac resuscitation or extracorporeal membrane oxygenation
             (ECMO).

          3. Lethal congenital anomalies.

          4. Congenital Diaphragmatic Hernia.

          5. Significant structural cardiac anomalies.

          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 alanine aminotransferase (ALT) values > 2 x
             upper limit of normal (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 lower limit of normal (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.