Persistent Pulmonary Hypertension of the NewbornPhase 3FUTURE 4NCT01389856
Persistent Pulmonary Hypertension of the Newborn
A Phase 3 study testing Bosentan in people with Persistent Pulmonary Hypertension of the Newborn, run by Actelion.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 hours to 7 days
- Conditions the study is for
- Persistent Pulmonary Hypertension of the Newborn
- What is being tested?
- Bosentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- No sites listed yet
- Study dates
- Dec 2011to Jan 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 hours to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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).
- Any condition precluding the use of a nasogastric/orogastric tube.
- Administration of prohibited medication prior to randomization.
About this study
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 Hypertension of the Newborn (PPHN)
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.
- Being tested
- Bosentan, Matching placebo
- Keywords
- Persistent pulmonary hypertension, newborn, PPHN
- Medical subject headings
- Persistent Fetal Circulation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
Also called Tracleer
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.
Matching placeboDrug
twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Bosentan Receives: Drug: Bosentan |
| 2 | Placebo comparator | Matching placebo Receives: Drug: Matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: From baseline to up to 21 days
Secondary outcomes (30)
Percentage of Patients Requiring Re-initiation of iNO Therapy
Re-initiation of iNO therapy following weaning from iNO therapy
Measured: From baseline to up to 21 days
Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment
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
Measured: From baseline to up to 14 days
Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration
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.
Measured: 3 hours
Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration
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.
Measured: 5 hours
Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration
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.
Measured: 12 hours
Change in Oxygenation Index (OI) From Baseline to 24 Hours Following Study Drug Administration
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.
Measured: 24 hours
Change in Oxygenation Index (OI) From Baseline to 48 Hours Following Study Drug Administration
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.
Measured: 48 hours
Change in Oxygenation Index (OI) From Baseline to 72 Hours Following Study Drug Administration
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.
Measured: 72 hours
Change in Arterial Blood Gas (ABG) pH From Baseline to 72 Hours Following Study Drug Administration
pH was determined in arterial blood samples at baseline and 72 h after the first study drug administration
Measured: 72 hours
Change in Arterial Blood Oxygen Saturation (SaO2) From Baseline to 72 Hours Following Study Drug Administration
SaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration
Measured: 72 hours
Change in Partial Pressure of Oxygen (PaO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration
PaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration
Measured: 72 hours
Change in Partial Pressure of Carbon Dioxide (PaCO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration
PaCO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration
Measured: 72 hours
Change in Pre-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration
Simultaneous pre- (right hand) and post-ductal (lower extremities) SpO2 were measured using pulse oximetry device at baseline and 72 h after the first study drug administration
Measured: 72 hours
Change in Post-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration
Simultaneous pre- (right hand) and post-ductal (lower extremities) SpO2 were measured using pulse oximetry device at baseline and 72 h after the first study drug administration
Measured: 72 hours
Change in Fraction of Inspired Oxygen (FiO2) From Baseline to 72 Hours Following Study Drug Administration
FiO2 was determined according to each study centers' standard procedure at baseline and 72 h after the first study drug administration
Measured: 72 hours
Maximum Whole Blood Concentration (Cmax) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Cmax was obtained directly from the measured concentrations. Cmax was corrected to a dose of 2 mg/kg bosentan (Cmaxc). The target dose was 2 mg/kg. However, as the smallest dose unit was 8 mg (quarter of a tablet), it was not possible to achieve the exact target dose in all patients. Therefore, Cmax was divided by the actual dose (in mg/kg) and multiplied by 2 mg/kg.
Measured: up to 12 hours
Cmax for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 5
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Cmax obtained directly from the measured concentrations . Cmax was corrected to a dose of 2 mg/kg bosentan (Cmaxc). The target dose was 2 mg/kg. However, as the smallest dose unit was 8 mg (quarter of a tablet), it was not possible to achieve the exact target dose in all patients. Therefore, Cmax was divided by the actual dose (in mg/kg) and multiplied by 2 mg/kg.
Measured: 12 hours
Time to Maximum Whole Blood Concentration (Tmax) for Bosentan on Day 1
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.
Measured: up to 12 hours
Tmax for Ro 47-8634 on Day 1
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.
Measured: up to 12 hours
Tmax for Ro 48-5033 on Day 1
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.
Measured: up to 12 hours
Tmax for Ro 64-1056 on Day 1
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.
Measured: up to 12 hours
Tmax for Bosentan on Day 5
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.
Measured: 12 hours
Tmax for Ro 47-8634 on Day 5
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.
Measured: 12 hours
Tmax for Ro 48-5033 on Day 5
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.
Measured: 12 hours
Tmax for Ro 64-1056 on Day 5
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.
Measured: 12 hours
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
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-12 Day 1 was calculated according to the trapezoidal rule using the measured concentration-time values above the limit of quantification.
Measured: 12 hours
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
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUCtau Day 5 was calculated according to the trapezoidal rule using the measured concentration-time values above the limit of quantification.
Measured: 5 days
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
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-24C Day 1 was calculated as a multiple of AUC0-12, (2 × AUC0-12 for 2 times daily dosing) corrected to 2 mg/kg.
Measured: 24 hours
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
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-24C Day 5 was calculated as a multiple of AUCtau, (2 × AUCtau for 2 times daily dosing) corrected to 2 mg/kg.
Measured: 24 hours
Accumulation Index (AI) for Bosentan
Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Days 1 and 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AI was calculated as the ratio AUCtau /AUC0-12 for the subjects having PK samples collected on Day 1 and Day 5 and with AUC0-12 > 0 ng.h/mL.
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2011 (estimated)
- Study startDec 2011
- Primary completionDec 2013
- Study completionJan 2014
Why it stopped: To be compliant with the timelines as agreed with Paediatric Committee (PC) within the Paediatric Investigational Plan
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Persistent Pulmonary Hypertension of the NewbornStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01389856
- Sponsor's protocol ID
- AC-052-391
- Acronym
- FUTURE 4
- Status last verified
- Jan 2025
- First submitted
- 30 Jun 2011
- Last updated
- 4 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27502103
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Hypertension of the Newborn (PPHN)
- ClinicalTrials.gov ID
- NCT01389856
- Acronym / sponsor ID
- FUTURE 4 / AC-052-391
- Keywords
- Persistent pulmonary hypertension, newborn, PPHN
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: To be compliant with the timelines as agreed with Paediatric Committee (PC) within the Paediatric Investigational Plan
- Enrolment
- 23 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- Dec 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 8 Jul 2011 (estimated)
- Results
- Posted 23 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: BosentanBosentan |
| 2 | Placebo comparator | Drug: Matching placeboMatching placebo |
Who may qualify
- Ages
- 12 hours to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BosentanAlso: Tracleer2 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. | Drug | 1 |
| Matching placebotwice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube. | Drug | 2 |
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
30 secondary outcomes
Percentage of Patients Requiring Re-initiation of iNO Therapy
Time frame: From baseline to up to 21 days
Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment
Time frame: From baseline to up to 14 days
Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration
Time frame: 3 hours
Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration
Time frame: 5 hours
Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration
Time frame: 12 hours
Change in Oxygenation Index (OI) From Baseline to 24 Hours Following Study Drug Administration
Time frame: 24 hours
Change in Oxygenation Index (OI) From Baseline to 48 Hours Following Study Drug Administration
Time frame: 48 hours
Change in Oxygenation Index (OI) From Baseline to 72 Hours Following Study Drug Administration
Time frame: 72 hours
Change in Arterial Blood Gas (ABG) pH From Baseline to 72 Hours Following Study Drug Administration
Time frame: 72 hours
Change in Arterial Blood Oxygen Saturation (SaO2) From Baseline to 72 Hours Following Study Drug Administration
Time frame: 72 hours
Change in Partial Pressure of Oxygen (PaO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration
Time frame: 72 hours
Change in Partial Pressure of Carbon Dioxide (PaCO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration
Time frame: 72 hours
Change in Pre-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration
Time frame: 72 hours
Change in Post-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration
Time frame: 72 hours
Change in Fraction of Inspired Oxygen (FiO2) From Baseline to 72 Hours Following Study Drug Administration
Time frame: 72 hours
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
Cmax for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 5
Time frame: 12 hours
Time to Maximum Whole Blood Concentration (Tmax) for Bosentan on Day 1
Time frame: up to 12 hours
Tmax for Ro 47-8634 on Day 1
Time frame: up to 12 hours
Tmax for Ro 48-5033 on Day 1
Time frame: up to 12 hours
Tmax for Ro 64-1056 on Day 1
Time frame: up to 12 hours
Tmax for Bosentan on Day 5
Time frame: 12 hours
Tmax for Ro 47-8634 on Day 5
Time frame: 12 hours
Tmax for Ro 48-5033 on Day 5
Time frame: 12 hours
Tmax for Ro 64-1056 on Day 5
Time frame: 12 hours
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
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
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
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
Accumulation Index (AI) for Bosentan
Time frame: 5 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27502103Steinhorn 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.
Related trials for Persistent Pulmonary Hypertension of the Newborn
Recruiting
Effect of Melatonin on Pulmonary Hypertension in Full Term Neonates
Congenital Peumonia, Persistent Pulmonary Hypertension of Newborn
Not yet recruitingObservational study
Post Market Clinical Follow-up to Assess the Portable Nitric Oxide Generation and Delivery System (INOwill N200) for the Treatment of Neonatal Hypoxic Respiratory Failure Complicated by Pulmonary Hypertension
Persistent Pulmonary Hypertension of the Newborn, Hypoxic Respiratory Failure
Not yet recruitingObservational study
Predictors of Outcomes in Pulmonary Hypertension of the Newborn
Hypertension, Pulmonary, Infant, Newborn, Diseases
Recruiting
Close Loop Smart Weaning for INO With PPHN
Persistent Pulmonary Hypertension of the Newborn, Inhaled Nitric Oxide
Active, not recruiting
Preductal Oxygen Saturation Target in Term and Late Preterm Neonates With Hypoxemic Respiratory Failure or Pulmonary Hypertension
Persistent Pulmonary Hypertension of the Newborn, Hypoxemic Respiratory Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bosentan in people with Persistent Pulmonary Hypertension of the Newborn, run by Actelion.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With Treatment Failure (time frame: From baseline to up to 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01389856, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.