PPHNPhase 2NCT01069861
Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN)
A Phase 2 study testing sildanefil in people with PPHN and Persistent Pulmonary Hypertension of the Newborn, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 1 site in United Kingdom.
Trial summary
Sildenafil is efficacious in newborns with persistent pulmonary hypertension and its use will reduce the need for inhaled nitric oxide. Read more about this study
- Who is it for?
- Ages 1 hour to 72 hours
- Conditions the study is for
- PPHN, Persistent Pulmonary Hypertension of the Newborn, Hypoxic Respiratory Failure
- What is being tested?
- sildanefil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2010to Nov 2011
- Phase
- Phase 2
- 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 1 hour to 72 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 72 hours of age; and > or = to 34 weeks gestational age.
- Persistent Pulmonary Hypertension of the Newborn or Hypoxic respiratory failure associated with:
- Idiopathic PPHN or
- Meconium aspiration syndrome or
- Sepsis or
- Pneumonia
- Oxygenation Index (OI) >15 and <60 calculated
Who cannot join
- Patients already receiving inhaled nitric oxide (iNO) on referral.
- Prior or immediate need for full Cardio Pulmonary Resuscitation or Extracorporeal Membrane Oxygenation (ECMO).
- Life threatening or lethal congenital anomaly.
- Large left to right intracardiac or ductal shunting (diagnosed from echocardiogram on admission to GOSH).
- Clinically significant active seizures as per clinical judgment.
- Bleeding diathesis as per clinical judgment
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Great Ormond Street Hospital, Paediatric Intensive Care
London, WC1N 3JH
About this study
Official title: A Single Arm Single Centre Study To Investigate Safety And Efficacy Of Sildenafil In Near Term And Term Newborns With Persistent Pulmonary Hypertension Of The Newborn (PPHN)
Sildenafil is efficacious in newborns with persistent pulmonary hypertension and its use will reduce the need for inhaled nitric oxide.
Read the detailed description
Letter to investigator dated 18 June 2012 that study was to be terminated. Study terminated due to evolved and widespread use of standard of care, relevance of study questioned. No safety reasons or issues.
- Being tested
- sildanefil
- Keywords
- PPHN, neonates, sildanefil IV
- 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.
sildanefilDrug
Intravenous sildenafil citrate will be administered as a loading dose of 0.1 mg/kg given over 30 minutes. This will be followed by a maintenance treatment consisting of an intravenous infusion of 0.03 mg/kg/hr. The duration of the infusion will be determined by the need of the individual patient, but will be reviewed at Day 7 if still ongoing, and will not continue past Day 14.
| Study group | Role | What they receive |
|---|---|---|
| one | Experimental | Not described Receives: Drug: sildanefil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO)
Percentage of participants who required standard therapy (iNO or ECMO) after failure of study treatment.
Measured: From start of infusion (baseline) up to Day 14
Number of Participants With Adverse Events (AEs) Based on Severity
AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE:AE resulting in any of following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience; persistent/significant disability/incapacity; congenital anomaly. Severity criteria: "mild=does not interfere with participant's usual function; moderate=interferes to some extent with participant's usual function and severe=interferes significantly with participant's usual function".
Measured: Baseline up to 28 days after last dose
Number of Participants With Abnormal Laboratory Data
Criteria for potentially clinically significant (PCS) laboratory values: hematocrit 29.2 percent (%); white blood cell (WBC) count 5.0*10^3, lymphocyte absolute 0.88*10^3, total neutrophils absolute 12.07*10^3, eosinophils absolute 0.50*10^3 per cubic millimeter (/mm^3); calcium 6.8 milligram/deciliter (mg/dL); venous bicarbonate 47.0 milliequivalent/liter (meq/L).
Measured: Screening, once daily for 3 days, every 48 hours thereafter till the end of infusion (up to Day 14)
Secondary outcomes (7)
Change From Baseline in Oxygenation Index at Hour 6 and 12
Oxygenation Index (OI) was calculated as the product of fraction of inspired oxygen (FiO2) and Mean Airway Pressure divided by partial pressure of oxygen in arterial blood [(FiO2*Mean Airway Pressure)/PaO2] measured in centimeter of water/millimeter of mercury (cmH2O/mmHg). FiO2 is the measure of oxygen concentration that is breathed. Mean airway pressure is defined as an average of the airway pressure throughout the respiratory cycle. PaO2 is the measure of oxygen level in the arterial blood.
Measured: Baseline, Hour 6, 12
Change From Baseline in Differential Saturation (Pre- And Post-ductal) at Hour 6 and 12
Differential oxygenation saturation between preductal and postductal sites as measured by pulse oximetry. A difference of greater than (>) 5 percent (%) to 10% in saturation indicates right-to-left shunt through the ductus arteriosus. Oxygenation saturation is measured as percentage of hemoglobin binding sites occupied by oxygen in the blood.
Measured: Baseline, Hour 6, 12
Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to the Fraction of Inspired Oxygen (P/F) at Hour 6 and 12
The ratio of partial pressure of arterial oxygen and fraction of inspired oxygen is a comparison between the oxygen level in the arterial blood and the oxygen concentration that is breathed. It helps to determine the degree of any problems with how the lungs transfer oxygen to the blood.
Measured: Baseline, Hour 6, 12
Duration of Mechanical Ventilation
The number of days from the start to the stop of mechanical ventilation, if multiple ventilations occurred during the follow-up, the sum of the duration of each ventilation was used for analyses. Mechanical ventilation was defined as use of mechanical assistance or replacement of spontaneous breathing.
Measured: Baseline up to 28 days after last dose
Time to Receipt of Standard Therapy (Inhaled Nitric Oxide [iNO] or Extracorporeal Membrane Oxygenation [ECMO])
Time from start of treatment up to introduction of standard therapy. If participants did not receive standard therapy within 14 days after initiation of the study treatment, then Day 14 was the censoring time.
Measured: Baseline up to 28 days after last dose
Population Pharmacokinetics of Sildenafil
Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Measured: Pre-dose, 5 and 30 minutes post-loading infusion, within 48 to 72, 96 to 120 hours during infusion, within 4 to 8, 18 to 24 and 44 to 48 hours post-maintenance infusion
Maximum Observed Plasma Concentration (Cmax) of Sildenafil Metabolite (UK-103320)
Measured: Pre-dose, 5 and 30 minutes post-loading infusion, within 48 to 72, 96 to 120 hours during infusion, within 4 to 8, 18 to 24 and 44 to 48 hours post-maintenance infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2010 (estimated)
- Study startDec 2010
- Primary completionNov 2011
- Study completionNov 2011
Why it stopped: See termination reason in detailed description.
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.
- Other trials for PPHNStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01069861
- Sponsor's protocol ID
- A1481276
- Status last verified
- Jan 2021
- First submitted
- 15 Feb 2010
- Last updated
- 1 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm Single Centre Study To Investigate Safety And Efficacy Of Sildenafil In Near Term And Term Newborns With Persistent Pulmonary Hypertension Of The Newborn (PPHN)
- ClinicalTrials.gov ID
- NCT01069861
- Acronym / sponsor ID
- A1481276
- Keywords
- PPHN, neonates, sildanefil IV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 17 Feb 2010 (estimated)
- Results
- Posted 3 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sildenafil is efficacious in newborns with persistent pulmonary hypertension and its use will reduce the need for inhaled nitric oxide.
Detailed description
Letter to investigator dated 18 June 2012 that study was to be terminated. Study terminated due to evolved and widespread use of standard of care, relevance of study questioned. No safety reasons or issues.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| one | Experimental | Drug: sildanefil |
Who may qualify
- Ages
- 1 hour to 72 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 72 hours of age; and > or = to 34 weeks gestational age.
- Persistent Pulmonary Hypertension of the Newborn or Hypoxic respiratory failure associated with:
- Oxygenation Index (OI) >15 and <60 calculated
Key exclusion criteria (6 listed)
- Patients already receiving inhaled nitric oxide (iNO) on referral.
- Prior or immediate need for full Cardio Pulmonary Resuscitation or Extracorporeal Membrane Oxygenation (ECMO).
- Life threatening or lethal congenital anomaly.
- Large left to right intracardiac or ductal shunting (diagnosed from echocardiogram on admission to GOSH).
- Clinically significant active seizures as per clinical judgment.
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 |
|---|---|---|
| sildanefilIntravenous sildenafil citrate will be administered as a loading dose of 0.1 mg/kg given over 30 minutes. This will be followed by a maintenance treatment consisting of an intravenous infusion of 0.03 mg/kg/hr. The duration of the infusion will be determined by the need of the individual patient, but will be reviewed at Day 7 if still ongoing, and will not continue past Day 14. | Drug | one |
Primary outcome
Percentage of Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO)
Time frame: From start of infusion (baseline) up to Day 14
Percentage of participants who required standard therapy (iNO or ECMO) after failure of study treatment.
Number of Participants With Adverse Events (AEs) Based on Severity
Time frame: Baseline up to 28 days after last dose
AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE:AE resulting in any of following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience; persistent/significant disability/incapacity; congenital anomaly. Severity criteria: "mild=does not interfere with participant's usual function; moderate=interferes to some extent with participant's usual function and severe=interferes significantly with participant's usual function".
Number of Participants With Abnormal Laboratory Data
Time frame: Screening, once daily for 3 days, every 48 hours thereafter till the end of infusion (up to Day 14)
Criteria for potentially clinically significant (PCS) laboratory values: hematocrit 29.2 percent (%); white blood cell (WBC) count 5.0*10^3, lymphocyte absolute 0.88*10^3, total neutrophils absolute 12.07*10^3, eosinophils absolute 0.50*10^3 per cubic millimeter (/mm^3); calcium 6.8 milligram/deciliter (mg/dL); venous bicarbonate 47.0 milliequivalent/liter (meq/L).
7 secondary outcomes
Change From Baseline in Oxygenation Index at Hour 6 and 12
Time frame: Baseline, Hour 6, 12
Change From Baseline in Differential Saturation (Pre- And Post-ductal) at Hour 6 and 12
Time frame: Baseline, Hour 6, 12
Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to the Fraction of Inspired Oxygen (P/F) at Hour 6 and 12
Time frame: Baseline, Hour 6, 12
Duration of Mechanical Ventilation
Time frame: Baseline up to 28 days after last dose
Time to Receipt of Standard Therapy (Inhaled Nitric Oxide [iNO] or Extracorporeal Membrane Oxygenation [ECMO])
Time frame: Baseline up to 28 days after last dose
Population Pharmacokinetics of Sildenafil
Time frame: Pre-dose, 5 and 30 minutes post-loading infusion, within 48 to 72, 96 to 120 hours during infusion, within 4 to 8, 18 to 24 and 44 to 48 hours post-maintenance infusion
Maximum Observed Plasma Concentration (Cmax) of Sildenafil Metabolite (UK-103320)
Time frame: Pre-dose, 5 and 30 minutes post-loading infusion, within 48 to 72, 96 to 120 hours during infusion, within 4 to 8, 18 to 24 and 44 to 48 hours post-maintenance infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Effect of a Parenteral Emulsion With Omega3 on Neonates With PPHN and CDH
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Recruiting
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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
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Not yet recruitingObservational study
Predictors of Outcomes in Pulmonary Hypertension of the Newborn
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RecruitingPhase 4
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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.
Pfizer CT.gov Call Center study director
Pfizer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sildanefil in people with PPHN and Persistent Pulmonary Hypertension of the Newborn, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 1 site in United Kingdom.
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 7 inclusion and 6 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 1 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Dec 2012). 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 Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO) (time frame: From start of infusion (baseline) up to Day 14). 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?
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 1 Feb 2021.