Clinical Trial: Persistent Pulmonary Hypertension of the Newborn

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Multicenter, Double-blind, Placebo-controlled, Randomized, Prospective Study of Bosentan as Adjunctive Therapy to Inhaled Nitric Oxide in the Management of Persistent Pulmonary H

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.

Detailed Summary:
Sponsor: Actelion

Current Primary Outcome:

  • Percentage of Patients With Treatment Failure [ Time Frame: From baseline to up to 21 days ]
    Treatment failure was defined as the need for extra corporeal membrane oxygenation or initiation of alternative pulmonary vasodilator treatment
  • Time to Complete Weaning From iNO [ Time Frame: From baseline to up to 21 days ]
    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
  • Time to Complete Weaning From Mechanical Ventilation [ Time Frame: From baseline to up to 21 days ]
    Calculated from the time from first study drug administration to complete weaning from mechanical ventilation


Original Primary Outcome: Proportion of Patients With Treatment Failure [ Time Frame: From baseline to up to 14 days ]

Exploratory Endpoint:

Proportion of patients with treatment failure:

  • Need for extra corporeal membrane oxygenation (ECMO) or
  • Initiation of alternative pulmonary vasodilator


Current Secondary Outcome:

  • Percentage of Patients Requiring Re-initiation of iNO Therapy [ Time Frame: From baseline to up to 21 days ]
    Re-initiation of iNO therapy following weaning from iNO therapy
  • Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment [ Time Frame: From baseline to up to 14 days ]

    The presence of PH was assessed by echocardiography. PH was reported as 'present' if at least one of the following criteria was met:

    • Shunt through ductus arteriosus was either 'predominant right to left' or 'bidirectional'
    • Shunt through foramen ovale was either 'predominant right to left' or 'bidirectional'
    • Marked right ventricular dilation was ticked 'present'
    • Paradoxical shift of intraventricular septum was ticked 'present'
    • Right ventricular systolic pressure (mmHg) was > 2/3 of the reported systemic blood pressure
  • Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration [ Time Frame: 3 hours ]
    The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
  • Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration [ Time Frame: 5 hours ]
    The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
  • Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration [ Time Frame: 12 hours ]
    The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
  • Change in Oxygenation Index (OI) From Baseline to 24 Hours Following Study Drug Administration [ Time Frame: 24 hours ]
    The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
  • Change in Oxygenation Index (OI) From Baseline to 48 Hours Following Study Drug Administration [ Time Frame: 48 hours ]
    The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
  • Change in Oxygenation Index (OI) From Baseline to 72 Hours Following Study Drug Administration [ Time Frame: 72 hours ]
    The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.
  • Change in Arterial Blood Gas (ABG) pH From Baseline to 72 Hours Following Study Drug Administration [ Time Frame: 72 hours ]
    pH was determined in arterial blood samples at baseline and 72 h after the first study drug administration
  • Change in Arterial Blood Oxygen Saturation (SaO2) From Baseline to 72 Hours Following Study Drug Administration [ Time Frame: 72 hours ]
    SaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration
  • Change in Partial Pressure of Oxygen (PaO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration [ Time Frame: 72 hours ]
    PaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration
  • Change in Partial Pressure of Carbon Dioxide (PaCO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration [ Time Frame: 72 hours ]
    PaCO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration
  • Change in Pre-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration [ Time Frame:&

    Original Secondary Outcome: Time to complete weaning from inhaled nitric oxide (iNO) [ Time Frame: From baseline to up to 14 days ]

    Exploratory Endpoint:

    Time to complete weaning from inhaled nitric oxide (iNO)



    Information By: Actelion

    Dates:
    Date Received: June 30, 2011
    Date Started: December 2011
    Date Completion:
    Last Updated: April 9, 2015
    Last Verified: April 2015