Back to resultsStudy To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN)
Primary Purpose
PPHN, Persistent Pulmonary Hypertension of the Newborn, Hypoxic Respiratory Failure
Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
sildanefil
Sponsored by
About this trial
This is an interventional treatment trial for PPHN focused on measuring PPHN, neonates, sildanefil IV
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Great Ormond Street Hospital, Paediatric Intensive Care
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
one
Arm Description
Outcomes
Primary Outcome Measures
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.
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".
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).
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Maximum Observed Plasma Concentration (Cmax) of Sildenafil Metabolite (UK-103320)
Full Information
NCT ID
NCT01069861
First Posted
February 15, 2010
Last Updated
January 28, 2021
Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01069861
Brief Title
Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
December 2010 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PPHN, Persistent Pulmonary Hypertension of the Newborn, Hypoxic Respiratory Failure
Keywords
PPHN, neonates, sildanefil IV
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
one
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
sildanefil
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO)
Description
Percentage of participants who required standard therapy (iNO or ECMO) after failure of study treatment.
Time Frame
From start of infusion (baseline) up to Day 14
Title
Number of Participants With Adverse Events (AEs) Based on Severity
Description
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".
Time Frame
Baseline up to 28 days after last dose
Title
Number of Participants With Abnormal Laboratory Data
Description
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).
Time Frame
Screening, once daily for 3 days, every 48 hours thereafter till the end of infusion (up to Day 14)
Secondary Outcome Measure Information:
Title
Change From Baseline in Oxygenation Index at Hour 6 and 12
Description
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.
Time Frame
Baseline, Hour 6, 12
Title
Change From Baseline in Differential Saturation (Pre- And Post-ductal) at Hour 6 and 12
Description
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.
Time Frame
Baseline, Hour 6, 12
Title
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
Description
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.
Time Frame
Baseline, Hour 6, 12
Title
Duration of Mechanical Ventilation
Description
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.
Time Frame
Baseline up to 28 days after last dose
Title
Time to Receipt of Standard Therapy (Inhaled Nitric Oxide [iNO] or Extracorporeal Membrane Oxygenation [ECMO])
Description
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.
Time Frame
Baseline up to 28 days after last dose
Title
Population Pharmacokinetics of Sildenafil
Description
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.
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
Title
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
Other Pre-specified Outcome Measures:
Title
Duration of Study Medication
Description
The duration of the infusion was determined as per investigator's discretion up to Day 7 or Day 14.
Time Frame
Baseline up to Day 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Hour
Maximum Age & Unit of Time
72 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Great Ormond Street Hospital, Paediatric Intensive Care
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A1481276&StudyName=Study%20To%20Investigate%20Safety%20And%20Efficacy%20Of%20Sildenafil%20In%20The%20Newborns%20With%20Persistent%20Pulmonary%20Hypertension%20%28PPHN%29
Description
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Learn more about this trial
Study To Investigate Safety And Efficacy Of Sildenafil In The Newborns With Persistent Pulmonary Hypertension (PPHN)
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