Persistent Pulmonary Hypertension of the Newborn (FUTURE 4)

This study has been terminated.
(To be compliant with the timelines as agreed with Paediatric Committee (PC) within the Paediatric Investigational Plan)
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01389856
First received: June 30, 2011
Last updated: April 9, 2015
Last verified: April 2015
Results First Received: March 9, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Persistent Pulmonary Hypertension of the Newborn
Interventions: Drug: Bosentan
Drug: Matching placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient, first visit was 8 December 2011 and last patient, last visit was 5 December 2013. The investigational sites were tertiary care centers with neonatal intensive care unit facilities at which inhaled nitric oxide (iNO) was used as standard of care for persistent pulmonary hypertension of the newborn (PPHN).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Term or near-term (gestational age > 34 weeks) hypoxic newborns with respiratory distress refractory to supplemental oxygen were considered, provided they had no significant structural cardiac anomalies documented in the pre-natal period and had no immediate need for extra corporeal membrane oxygenation (ECMO).

Reporting Groups
  Description
Bosentan

Bosentan

Bosentan: 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.

Placebo

Matching placebo

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


Participant Flow:   Overall Study
    Bosentan     Placebo  
STARTED     13 [1]   8 [2]
COMPLETED     13     8  
NOT COMPLETED     0     0  
[1] Randomized and treated. An additional 2 patients were randomized but not treated.
[2] Randomized and treated.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized and treated patients

Reporting Groups
  Description
Bosentan

Bosentan

Bosentan: 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.

Placebo

Matching placebo

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

Total Total of all reporting groups

Baseline Measures
    Bosentan     Placebo     Total  
Number of Participants  
[units: participants]
  13     8     21  
Age  
[units: days]
Median (Full Range)
  1.4    (0.6 to 5.6)     1.7    (0.6 to 5.9)     1.4    (0.6 to 5.9)  
Gender  
[units: participants]
     
Female     9     6     15  
Male     4     2     6  
Race/Ethnicity, Customized  
[units: participants]
     
Caucasian/white     11     6     17  
Asian     1     0     1  
Hispanic     1     1     2  
Other     0     1     1  
Region of Enrollment  
[units: participants]
     
Czech Republic     1     1     2  
France     1     0     1  
Korea, Republic of     1     0     1  
Poland     5     3     8  
United Kingdom     4     2     6  
United States     1     2     3  
Gestational age  
[units: weeks]
Median (Full Range)
  40.0    (36.0 to 41.0)     38.5    (36.0 to 42.0)     39.0    (36.0 to 42.0)  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Patients With Treatment Failure   [ Time Frame: From baseline to up to 21 days ]

2.  Primary:   Time to Complete Weaning From iNO   [ Time Frame: From baseline to up to 21 days ]

3.  Primary:   Time to Complete Weaning From Mechanical Ventilation   [ Time Frame: From baseline to up to 21 days ]

4.  Secondary:   Percentage of Patients Requiring Re-initiation of iNO Therapy   [ Time Frame: From baseline to up to 21 days ]

5.  Secondary:   Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment   [ Time Frame: From baseline to up to 14 days ]

6.  Secondary:   Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration   [ Time Frame: 3 hours ]

7.  Secondary:   Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration   [ Time Frame: 5 hours ]

8.  Secondary:   Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration   [ Time Frame: 12 hours ]

9.  Secondary:   Change in Oxygenation Index (OI) From Baseline to 24 Hours Following Study Drug Administration   [ Time Frame: 24 hours ]

10.  Secondary:   Change in Oxygenation Index (OI) From Baseline to 48 Hours Following Study Drug Administration   [ Time Frame: 48 hours ]

11.  Secondary:   Change in Oxygenation Index (OI) From Baseline to 72 Hours Following Study Drug Administration   [ Time Frame: 72 hours ]

12.  Secondary:   Change in Arterial Blood Gas (ABG) pH From Baseline to 72 Hours Following Study Drug Administration   [ Time Frame: 72 hours ]

13.  Secondary:   Change in Arterial Blood Oxygen Saturation (SaO2) From Baseline to 72 Hours Following Study Drug Administration   [ Time Frame: 72 hours ]

14.  Secondary:   Change in Partial Pressure of Oxygen (PaO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration   [ Time Frame: 72 hours ]

15.  Secondary:   Change in Partial Pressure of Carbon Dioxide (PaCO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration   [ Time Frame: 72 hours ]

16.  Secondary:   Change in Pre-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration   [ Time Frame: 72 hours ]

17.  Secondary:   Change in Post-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration   [ Time Frame: 72 hours ]

18.  Secondary:   Change in Fraction of Inspired Oxygen (FiO2) From Baseline to 72 Hours Following Study Drug Administration   [ Time Frame: 72 hours ]

19.  Secondary:   Maximum Whole Blood Concentration (Cmax) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1   [ Time Frame: up to 12 hours ]

20.  Secondary:   Cmax for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 5   [ Time Frame: 12 hours ]

21.  Secondary:   Time to Maximum Whole Blood Concentration (Tmax) for Bosentan on Day 1   [ Time Frame: up to 12 hours ]

22.  Secondary:   Tmax for Ro 47-8634 on Day 1   [ Time Frame: up to 12 hours ]

23.  Secondary:   Tmax for Ro 48-5033 on Day 1   [ Time Frame: up to 12 hours ]

24.  Secondary:   Tmax for Ro 64-1056 on Day 1   [ Time Frame: up to 12 hours ]

25.  Secondary:   Tmax for Bosentan on Day 5   [ Time Frame: 12 hours ]

26.  Secondary:   Tmax for Ro 47-8634 on Day 5   [ Time Frame: 12 hours ]

27.  Secondary:   Tmax for Ro 48-5033 on Day 5   [ Time Frame: 12 hours ]

28.  Secondary:   Tmax for Ro 64-1056 on Day 5   [ Time Frame: 12 hours ]

29.  Secondary:   Area Under the Concentration-time Curve Over a Period of 12 h (AUC0-12 Day 1)) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1   [ Time Frame: 12 hours ]

30.  Secondary:   Area Under the Concentration-time Curve Over a Dosing Interval at Steady State on Day 5 (AUCtau) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056   [ Time Frame: 5 days ]

31.  Secondary:   Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 1 (AUC0-24C Day 1) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056   [ Time Frame: 24 hours ]

32.  Secondary:   Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 5 (AUC0-24C Day 5) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056   [ Time Frame: 24 hours ]

33.  Secondary:   Accumulation Index (AI) for Bosentan   [ Time Frame: 5 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pegah Nowbakht/Senior Clinical Trial Scientist
Organization: Actelion Pharmaceuticals Ltd
phone: +41 61 565 68 41
e-mail: pegah.nowbakht@actelion.com


No publications provided


Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01389856     History of Changes
Other Study ID Numbers: AC-052-391
Study First Received: June 30, 2011
Results First Received: March 9, 2015
Last Updated: April 9, 2015
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Ethikkommission
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
United States: Food and Drug Administration
United States: Institutional Review Board
Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Poland: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Korea: Institutional Review Board
Korea: Ministry of Food and Drug Safety
Singapore: Institutional Review Board
Singapore: Health Sciences Authority
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation