Persistent Pulmonary Hypertension of the Newborn

NCT01389856 | Terminated Phase 3 Results DMC

• 1 other identifier: AC-052-391
• Study Type: interventional
• Target: 23
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Persistent Pulmonary Hypertension of the Newborn

Keywords

Persistent pulmonary hypertension, newborn; PPHN

Outcome Measures

Primary Outcomes (3)

• Percentage of Patients With Treatment Failure

  Treatment failure was defined as the need for extra corporeal membrane oxygenation or initiation of alternative pulmonary vasodilator treatment

  From baseline to up to 21 days

• Time to Complete Weaning From iNO

  Calculated from the time from first study drug administration to complete weaning from iNO. Weaning from iNO was considered complete if there was no requirement for the re-initiation of iNO within 24 h after stopping

  From baseline to up to 21 days

• Time to Complete Weaning From Mechanical Ventilation

  Calculated from the time from first study drug administration to complete weaning from mechanical ventilation

  From baseline to up to 21 days

Secondary Outcomes (30)

• Percentage of Patients Requiring Re-initiation of iNO Therapy

  From baseline to up to 21 days

• Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment

  From baseline to up to 14 days

• Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration

  3 hours

• Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration

  5 hours

• Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration

  12 hours

Study Arms (2)

1

EXPERIMENTAL

Bosentan

Drug: Bosentan

2

PLACEBO COMPARATOR

Matching placebo

Drug: Matching placebo

Interventions

Bosentan DRUG

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.

Also known as: Tracleer

1

Matching placebo DRUG

twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.

2

Eligibility Criteria

• Age: 12 Hours - 7 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed informed consent by the parent(s) or the legal representative(s).
• Term and near term newborns (gestational age \> 34 weeks).
• Post natal age ≥ 12 hours and \< 7 days.
• Weight at birth ≥ 2,000 g.
• Idiopathic PPHN or PPHN due to parenchymal lung disease
• Documented diagnosis of pulmonary hypertension (PH) confirmed by echocardiography.
• Need for continued inhaled nitric oxide (iNO) at a dose \> 10ppm after at least 4 hours of continuous iNO treatment.
• 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.
• Mechanical ventilation with fraction of inspired oxygen (FiO2) ≥ 50% at randomization.

You may not qualify if:

• PH associated with conditions other than PPHN.
• Immediate need for cardiac resuscitation or extracorporeal membrane oxygenation (ECMO).
• Lethal congenital anomalies.
• Congenital Diaphragmatic Hernia.
• Significant structural cardiac anomalies.
• Medically significant pneumothorax.
• Active seizures.
• Expected duration of mechanical ventilation of less than 48 hours.
• Mean systemic blood pressure \< 35 mmHg despite therapy with volume infusions and cardiotonic support.
• Hepatic failure or all conditions with alanine aminotransferase (ALT) values \> 2 x upper limit of normal (ULN).
• Renal function impairment such as serum creatinine \> 3 x ULN or anuria.
• Known intracranial hemorrhage grade III or IV.
• Either hemoglobin or hematocrit level \< 75% of the lower limit of normal (LLN).
• Thrombocytopenia (platelet count \< 50,000 cells /µL).
• Leukopenia (WBC \< 2,500 cells/ µL).

Sponsors & Collaborators

• Actelion: lead

Related Publications (1)

• Steinhorn RH, Fineman J, Kusic-Pajic A, Cornelisse P, Gehin M, Nowbakht P, Pierce CM, Beghetti M; FUTURE-4 study investigators. Bosentan as Adjunctive Therapy for Persistent Pulmonary Hypertension of the Newborn: Results of the Randomized Multicenter Placebo-Controlled Exploratory Trial. J Pediatr. 2016 Oct;177:90-96.e3. doi: 10.1016/j.jpeds.2016.06.078. Epub 2016 Aug 5.

  PMID: 27502103 DERIVED

MeSH Terms

Conditions

Persistent Fetal Circulation Syndrome

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pegah Nowbakht/Senior Clinical Trial Scientist
• Organization: Actelion Pharmaceuticals Ltd

pegah.nowbakht@actelion.com

+41 61 565 68 41

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2011
• First Posted: July 8, 2011
• Study Start: December 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: January 1, 2014
• Last Updated: February 4, 2025
• Results First Posted: March 23, 2015

Record last verified: 2025-01