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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01389856




Registration number
NCT01389856
Ethics application status
Date submitted
30/06/2011
Date registered
8/07/2011
Date last updated
1/05/2015

Titles & IDs
Public title
Persistent Pulmonary Hypertension of the Newborn
Scientific title
Multicenter, Double-blind, Placebo-controlled, Randomized, Prospective Study of Bosentan as Adjunctive Therapy to Inhaled Nitric Oxide in the Management of Persistent Pulmonary Hypertension of the Newborn (PPHN)
Secondary ID [1] 0 0
AC-052-391
Universal Trial Number (UTN)
Trial acronym
FUTURE 4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Persistent Pulmonary Hypertension of the Newborn 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 0 0 0 0
Complications of newborn
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bosentan
Treatment: Drugs - Matching placebo

Experimental: 1 - Bosentan

Placebo comparator: 2 - Matching placebo


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Patients With Treatment Failure
Timepoint [1] 0 0
From baseline to up to 21 days
Primary outcome [2] 0 0
Time to Complete Weaning From iNO
Timepoint [2] 0 0
From baseline to up to 21 days
Primary outcome [3] 0 0
Time to Complete Weaning From Mechanical Ventilation
Timepoint [3] 0 0
From baseline to up to 21 days
Secondary outcome [1] 0 0
Percentage of Patients Requiring Re-initiation of iNO Therapy
Timepoint [1] 0 0
From baseline to up to 21 days
Secondary outcome [2] 0 0
Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment
Timepoint [2] 0 0
From baseline to up to 14 days
Secondary outcome [3] 0 0
Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration
Timepoint [3] 0 0
3 hours
Secondary outcome [4] 0 0
Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration
Timepoint [4] 0 0
5 hours
Secondary outcome [5] 0 0
Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration
Timepoint [5] 0 0
12 hours
Secondary outcome [6] 0 0
Change in Oxygenation Index (OI) From Baseline to 24 Hours Following Study Drug Administration
Timepoint [6] 0 0
24 hours
Secondary outcome [7] 0 0
Change in Oxygenation Index (OI) From Baseline to 48 Hours Following Study Drug Administration
Timepoint [7] 0 0
48 hours
Secondary outcome [8] 0 0
Change in Oxygenation Index (OI) From Baseline to 72 Hours Following Study Drug Administration
Timepoint [8] 0 0
72 hours
Secondary outcome [9] 0 0
Change in Arterial Blood Gas (ABG) pH From Baseline to 72 Hours Following Study Drug Administration
Timepoint [9] 0 0
72 hours
Secondary outcome [10] 0 0
Change in Arterial Blood Oxygen Saturation (SaO2) From Baseline to 72 Hours Following Study Drug Administration
Timepoint [10] 0 0
72 hours
Secondary outcome [11] 0 0
Change in Partial Pressure of Oxygen (PaO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration
Timepoint [11] 0 0
72 hours
Secondary outcome [12] 0 0
Change in Partial Pressure of Carbon Dioxide (PaCO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration
Timepoint [12] 0 0
72 hours
Secondary outcome [13] 0 0
Change in Pre-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration
Timepoint [13] 0 0
72 hours
Secondary outcome [14] 0 0
Change in Post-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration
Timepoint [14] 0 0
72 hours
Secondary outcome [15] 0 0
Change in Fraction of Inspired Oxygen (FiO2) From Baseline to 72 Hours Following Study Drug Administration
Timepoint [15] 0 0
72 hours
Secondary outcome [16] 0 0
Maximum Whole Blood Concentration (Cmax) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1
Timepoint [16] 0 0
up to 12 hours
Secondary outcome [17] 0 0
Cmax for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 5
Timepoint [17] 0 0
12 hours
Secondary outcome [18] 0 0
Time to Maximum Whole Blood Concentration (Tmax) for Bosentan on Day 1
Timepoint [18] 0 0
up to 12 hours
Secondary outcome [19] 0 0
Tmax for Ro 47-8634 on Day 1
Timepoint [19] 0 0
up to 12 hours
Secondary outcome [20] 0 0
Tmax for Ro 48-5033 on Day 1
Timepoint [20] 0 0
up to 12 hours
Secondary outcome [21] 0 0
Tmax for Ro 64-1056 on Day 1
Timepoint [21] 0 0
up to 12 hours
Secondary outcome [22] 0 0
Tmax for Bosentan on Day 5
Timepoint [22] 0 0
12 hours
Secondary outcome [23] 0 0
Tmax for Ro 47-8634 on Day 5
Timepoint [23] 0 0
12 hours
Secondary outcome [24] 0 0
Tmax for Ro 48-5033 on Day 5
Timepoint [24] 0 0
12 hours
Secondary outcome [25] 0 0
Tmax for Ro 64-1056 on Day 5
Timepoint [25] 0 0
12 hours
Secondary outcome [26] 0 0
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
Timepoint [26] 0 0
12 hours
Secondary outcome [27] 0 0
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
Timepoint [27] 0 0
5 days
Secondary outcome [28] 0 0
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
Timepoint [28] 0 0
24 hours
Secondary outcome [29] 0 0
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
Timepoint [29] 0 0
24 hours
Secondary outcome [30] 0 0
Accumulation Index (AI) for Bosentan
Timepoint [30] 0 0
5 days

Eligibility
Key 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.
Minimum age
12 Hours
Maximum age
7 Days
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Royal Children's Hospital, Department of Neonatology - Site 3001 - Parkville
Recruitment hospital [2] 0 0
Division of Neonatology, Mater Mothers' Hospital, Mater Health Services, Brisbane Ltd. - Site 3003 - South Brisbane
Recruitment postcode(s) [1] 0 0
- Parkville
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
South Carolina
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Czech Republic
State/province [4] 0 0
Prague
Country [5] 0 0
France
State/province [5] 0 0
Lille Cedex
Country [6] 0 0
France
State/province [6] 0 0
Paris cedex 12
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
Germany
State/province [8] 0 0
Berlin
Country [9] 0 0
Germany
State/province [9] 0 0
Köln
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul
Country [11] 0 0
Poland
State/province [11] 0 0
Lodz
Country [12] 0 0
Poland
State/province [12] 0 0
Poznan
Country [13] 0 0
Poland
State/province [13] 0 0
Warszawa
Country [14] 0 0
Russian Federation
State/province [14] 0 0
Moscow
Country [15] 0 0
Singapore
State/province [15] 0 0
Singapore
Country [16] 0 0
Switzerland
State/province [16] 0 0
Lausanne
Country [17] 0 0
Switzerland
State/province [17] 0 0
Lucerne
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Liverpool
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Norwich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.