Persistent Pulmonary Hypertension of the Newborn (FUTURE 4)

Actelion Pharmaceuticals

Status and phase: Terminated; Phase 3

Conditions: Persistent Pulmonary Hypertension of the Newborn

Treatments: Drug: Bosentan; Drug: Matching placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01389856

AC-052-391

Details and patient eligibility

About

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.

Enrollment: 23 patients

Sex: All

Ages: 12 hours to 7 days old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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23 participants in 2 patient groups, including a placebo group

1

Experimental group

Description:

Bosentan

Treatment:

Drug: Bosentan

2

Placebo Comparator group

Description:

Matching placebo

Treatment:

Drug: Matching placebo