Clinical Trial Results:
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)
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Summary
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EudraCT number |
2009-016248-37 |
Trial protocol |
GB |
Global end of trial date |
01 Nov 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Jun 2016
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First version publication date |
01 Aug 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
A1481276
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01069861 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Oct 2012
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Nov 2011
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
1. To determine the efficacy of intravenous (IV) Sildenafil in near term and term newborns with Persistent pulmonary hypertension of the newborn (PPHN) or with hypoxic respiratory failure and at risk for PPHN. The primary measure of efficacy will be the reduced need for Inhaled Nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO).
2. To assess the safety and tolerability of IV Sildenafil in near term and term newborns with PPHN or with hypoxic respiratory failure and at risk of developing PPHN.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Dec 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 4
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Worldwide total number of subjects |
4
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EEA total number of subjects |
4
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
4
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
The study started on 18 December 2010 and ended on 01 November 2011. Overall, 4 subjects were enrolled in United Kingdom. | ||||||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Sildenafil | ||||||||||||||
Arm description |
Sildenafil citrate administered, based on the need of individual subject. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Sildenafil
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Sildenafil citrate administered intravenously at a loading dose of 0.1 mg/kg over 30 minutes infusion followed by a maintenance dose of 0.03 mg/kg/hr intravenous infusion up to 14 days, based on the need of individual subject.
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Baseline characteristics reporting groups
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Reporting group title |
Sildenafil
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Reporting group description |
Sildenafil citrate administered, based on the need of individual subject. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sildenafil
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Reporting group description |
Sildenafil citrate administered, based on the need of individual subject. | ||
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End point title |
Percentage of Subjects Requiring Inhaled Nitric Oxide (iNO) or Extracorporeal Membrane Oxygenation (ECMO) [1] | ||||||||
End point description |
Percentage of subjects who required standard therapy (iNO or ECMO) after failure of study treatment.
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End point type |
Primary
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End point timeframe |
From start of infusion (baseline) up to Day 14
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Data for this pre-specified outcome measure was collected and reported in individual subject listings but not statistically summarized for analysis due to early study termination. |
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| Notes [2] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subjects With Adverse Events (AEs) Based on Severity [3] | ||||||
End point description |
AE:any untoward medical occurrence in subject who received study drug without regard to possibility of causal relationship. Serious Adverse Event (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 subject's usual function; moderate=interferes to some extent with subject's usual function and severe=interferes significantly with subject's usual function”.
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End point type |
Primary
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End point timeframe |
Baseline up to 28 days after last dose
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Data for this pre-specified outcome measure was collected and reported in individual subject listings but not statistically summarized for analysis due to early study termination. |
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| Notes [4] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Abnormal Laboratory Data [5] | ||||||
End point description |
Following laboratory parameters were to be analyzed: Hemoglobin, hematocrit, RBC count, platelet count, WBC count, total neutrophils, eosinophils, lymphocytes, urea, creatinine, calcium, sodium, potassium, chloride, total CO2 (bicarbonate), aspartate aminotransferase, Alanine transaminase, total bilirubin, conjugated bilirubin, alkaline phosphatase and total protein.
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End point type |
Primary
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End point timeframe |
Screening, once daily for 3 days, every 48 hours thereafter till the end of infusion (up to Day 14)
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Data for this pre-specified outcome measure was collected and reported in individual subject listings but not statistically summarized for analysis due to early study termination. |
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| Notes [6] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||
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End point title |
Change From Baseline in Oxygenation Index at Hour 6 and 12 | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline, Hour 6, 12
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| Notes [7] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Differential Saturation (Pre- And Post-ductal) at Hour 6 and 12 | ||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline, Hour 6, 12
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| Notes [8] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||
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End point 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 | ||||||||
End point description |
The ratio of partial pressure of arterial oxygen and fraction of inspired oxygen (PaO2 / FiO2 ) 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.
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End point type |
Secondary
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End point timeframe |
Baseline, Hour 6, 12
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| Notes [9] - Data for this Outcome Measure not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Mechanical Ventilation | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline up to 28 days after last dose
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| Notes [10] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Receipt of Standard Therapy (Inhaled Nitric Oxide [iNO] or Extracorporeal Membrane Oxygenation [ECMO]) | ||||||||
End point description |
Time from start of treatment up to introduction of standard therapy. If subjects did not receive standard therapy within 14 days after initiation of the study treatment, then Day 14 was the censoring time.
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End point type |
Secondary
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End point timeframe |
Baseline up to 28 days after last dose
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| Notes [11] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Observed Plasma Concentration (Cmax) of Sildenafil and Metabolite (UK-103320) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
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
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| Notes [12] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Population Pharmacokinetics of Sildenafil and Metabolite (UK-103320) | ||||||||
End point description |
Data for this Outcome Measure are not reported here because the analysis population also includes subjects who were not enrolled in this study.
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End point type |
Secondary
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End point timeframe |
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
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| Notes [13] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Study Medication | ||||||||
End point description |
The duration of the infusion was determined as per investigator’s discretion up to Day 7 or Day 14.
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to Day 14
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| Notes [14] - Data for this Outcome Measure was not reported due to early study termination. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to 28 days after last dose
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Adverse event reporting additional description |
Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another, or 1 subject may have experienced both a serious and nonserious event during study. 1 subject died due to 2 fatal SAEs: persistent fetal circulation and congenital pneumonia.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Sildenafil
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Reporting group description |
Sildenafil citrate administered intravenously at a loading dose of 0.1 mg/kg over 30 minutes infusion followed by a maintenance dose of 0.03 mg/kg/hr intravenous infusion up to 14 days, based on the need of individual subject. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was prematurely discontinued, therefore not all data was analyzed. | |||
