Back to results

A Study To Evaluate Safety And Efficacy Of IV Sildenafil In The Treatment Of Neonates With Persistent Pulmonary Hypertension Of The Newborn

Primary Purpose

Pulmonary Hypertension, Familial Persistent, of the Newborn

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

placebo

iv sildenafil

About this trial

This is an interventional treatment trial for Pulmonary Hypertension, Familial Persistent, of the Newborn focused on measuring persistent pulmonary hypertension, newborn, neonates, iv sildenafil, hypoxic respiratory failure and at risk of persistent pulmonary hypertension of the newborn

Eligibility Criteria

0 Days - 4 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Neonates with persistent pulmonary hypertension of the newborn
Age <=96 hours and >=34 weeks gestational age
Oxygenation Index >15 and <60
Concurrent treatment with inhaled nitric oxide and >=50% oxygen

Exclusion Criteria:

Prior or immediate need for extracorporeal membrane oxygenation or cardiopulmonary resuscitation
Expected duration of mechanical ventilation <48 hours
Profound hypoxemia
Life-threatening or lethal congenital anomaly

Sites / Locations

Arkansas Children's Hospital
University of California Davis Medical Center
University of California Davis
University of California Davis Medical Center
Children´s National Medical Center
Indiana University Health Methodist Hospital
Riley Hospital for Children at IU Health
Sydney and Lois Eskenazi Hospital
Children's Mercy Hospitals & Clinics
Duke University Medical Center (DUMC)
Fairview Hospital
Cleveland Clinic
OU Follow-Up Program, PREMIEr Clinic, Children's Hospital
OU Neonatal Intensive Care Unit at Children's Hospital
The University of Oklahoma Health Sciences Center
Henry Zarrow Neonatal Intensive Care Unit, Children's Hospital at Saint Francis
Warren Cancer Research Foundation
Vanderbilt Children's Hospital
Seattle Children's Research Institute
Seattle Childrens Hospital
Universitair Ziekenhuis Antwerpen
UZ Gent
CHUL du CHU de Quebec
Aarhus Universitetshospital, Skejby
Neonatalklinikken Rigshospitalet, 5024
Centre Hospitalier et Regional de Lille - Hopital Jeanne de Flandre
Centre Hospitalier et Régional de Lille,
Hôpital de la Conception Assistance Publique-Hôpitaux de Marseille
CHU Robert Debré
Hopital NECKER - Enfants Malades
University Hospital of Leipzig
Neonatologia Fondazione IRCCS Policlinico San Matteo
Radboud University Nijmegen Medical Centre
Erasmus MC, Sophia Children's hospital
Haukeland University Hospital
Hospital Sant Joan de Deu
Hospital General Universitario Gregorio Marañon
Karolinska University Hospital
St. Michael's Hospital
Leicester Royal Infirmary
Glenfield Hospital, University Hospitals of Leicester NHS Trust
Great Ormond Street Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

placebo

sildenafil

Arm Description

iv placebo of normal saline or 10% dextrose

Active study drug

Outcomes

Primary Outcome Measures

Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure

Time in days, on iNO treatment, for participants without iNO treatment failure, was calculated 14 days from the initiation of IV study drug or hospital discharge, whichever occurred first. iNO treatment failure was defined as need for additional treatment targeting PPHN, need for extra corporeal membrane oxygenation (ECMO), or death during the study.

Treatment Failure Rate

Treatment failure rate was defined as percentage of participants who needed additional treatment targeting PPHN, needed ECMO, or died during the study.

Secondary Outcome Measures

Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation

Time in days, from initiation of IV study drug to final weaning of mechanical ventilation among participants achieving final weaning of mechanical ventilation for PPHN was evaluated. Kaplan-Meier method was used for estimation. For participants with mechanical ventilation beyond 336 hours (14 days) from initiation of IV study drug, data was censored at 14 days.

Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure

Time in days, from initiation of IV study drug to first treatment failure (defined as need for additional treatment targeting PPHN, need for ECMO, or death) for participants with treatment failure was evaluated. Kaplan-Meier method was used for estimation. For participants without treatment failure by the endpoint assessment date, data was censored at the endpoint assessment date.

Percentage of Participants With Individual Components of Treatment Failure

Percentage of participants with individual components of treatment failure (need to start additional treatment targeting PPHN, need to start ECMO, or death) were evaluated. Some participants could have had multiple qualifying events for treatment failure.

Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion

Oxygenation index was calculated as the product of fraction of inspired oxygen (FiO2) and mean airway pressure divided by partial pressure of oxygen dissolved in arterial blood (PaO2) [(FiO2*mean airway pressure)/PaO2] measured in centimeter of water per 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 dissolved in the arterial blood.

Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion

Differential oxygenation saturation is a simple way to detect the right-to left shunting at ductus arteriosus using 2 pulse oximeters. It is the difference between pre-ductal and post-ductal sites pulse oxygen saturation (SpO2). Where, pre-duct refers to right upper extremity and post-duct refers to lower limb. 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 Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24

The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen is a ratio 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.

Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite

Cmax was obtained for Sildenafil and its major metabolite UK-103,320.

Total Plasma Clearance (CL) of Sildenafil and Its Metabolite

CL is volume of the body fluid/ plasma from which the drug or the metabolite is completely removed per unit time. CL was obtained for Sildenafil and its major metabolite UK-103,320.

Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite

Vc is the hypothetical volume into which a drug or a metabolite initially distributes upon administration. It was determined by using a population-based analysis, non-linear mixed-effects modeling (NONMEM), version 7.4.0. Vc was calculated for Sildenafil and its major metabolite, UK-103,320.

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent are events between first infusion of study drug and up to 31 days after end of study drug infusion (up to 45 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.

Number of Treatment-Emergent Adverse Events (AEs) According to Severity

AE: untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. Treatment-emergent are events between first infusion of study drug and up to 31 days after end of study drug infusion (up to 45 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Severity criteria: mild=did not interfere with subject's usual function; moderate=interfered to some extent with participant's usual function and severe=interfered significantly with participant's usual function. Missing baseline severities were imputed as mild.

Number of Participants With Laboratory Abnormalities

Criteria for laboratory values: Hematology: hemoglobin, hematocrit, red blood cell count <0.8*lower limit of normal (LLN), platelets<0.5*LLN, >1.75*upper limit of normal (ULN), white blood cells count <0.6*LLN, >1.5*ULN; Liver function: total and direct bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3.0*ULN, total protein <0.8*LLN, >1.2*ULN; Renal function: blood urea nitrogen, creatinine >1.3*ULN; Electrolytes: sodium <0.95*LLN, >1.05*ULN, potassium, chloride, calcium, bicarbonate (venous) <0.9*LLN, >1.1*ULN.

Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

Bayley-III assesses infant and toddler development across five domains: cognitive, language, motor, social-emotional (SE), and adaptive behavior (AB). Assessments of the cognitive, language, and motor domains conducted using items administered to the child; assessments of the SE and AB domains conducted using the primary caregiver's responses to a questionnaire. Score ranges: cognitive scale 0-91, language scale 0-97 and motor scale 0-132, where higher scores indicated better cognitive function, communication and motor skills respectively. Raw scores of cognitive, language and motor domains were converted to composite scores. Composite scores of cognitive, language and motor developmental scales ranged from a scale of 40 to 160, where higher score indicated stronger skills and abilities. In this outcome measure composite scores for infants and toddlers were reported at month 12 and 24.

Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

The Bayley-III assesses infant and toddler development across five domains: cognitive, language, motor, social-emotional (SE), and adaptive behavior (AB). Assessments of the cognitive, language, and motor domains conducted using items administered to the child; assessments of the SE and AB domains conducted using the primary caregiver's responses to a questionnaire. The questionnaire comprises the SE scale (35 items) and the AB scale (241 items). Raw scores of SE and AB were converted to composite scores. Composite scores for SE and AB scale ranged from 40 to 160, where higher scores indicated better social-emotional skills and adaptive behavior in child. In this outcome measure composite scores for parent/caregiver were reported at month 24.

Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination

Standard age-appropriate ophthalmological examinations were used to assess eye movement disorders (presence of amblyopia, strabismus, and nystagmus) at month 12 and 24. In this outcome measure, data have been reported for right and left eye separately. Rows according to eye movement disorder categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.

Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment

Standard age-appropriate ophthalmological examinations were used to assess visual acuity (performed differently for children able of verbal interaction) through visual acuity chart (VAC) quantitative, counting finger (CF), hand motion (HM), light perception (LP), no light perception (NLP) and missing at month 12 and 24. In this outcome measure, data have been reported for right and left eye separately. Rows according to visual acuity categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.

Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment

Standard age-appropriate ophthalmological examinations were used to assess visual acuity (performed differently for children unable of verbal interaction) through fixates and follows (included central, steady and maintained), light perception (wince to light), no light perception, and missing at month 12 and 24. In this outcome measure, data have been reported for right and left eye separately. Rows according to visual acuity categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.

Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart

Standard age-appropriate ophthalmological examinations were used to assess visual acuity (performed differently for children able of verbal interaction) at month 12 and 24. Visual acuity (VA) of verbal children was assessed for each eye using the Snellen method, where logarithm of minimum angle of resolution (logMAR) units were derived from the Snellen ratios. Participants had to read letters from the chart at a distance of 20 feet/6 meter or 4 meter. VA (Snellen ratio) = distance between the chart and participant, divided by distance at which participant was able to see/read chart without impairment; expressed as decimal, logMAR = log10 (1/decimal VA). In this outcome measure, data have been reported for right and left eye separately.

Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments

Standard age-appropriate ophthalmological examinations were used to assess examination of anterior and posterior chamber for abnormality in lids, conjunctiva, cornea, anterior chamber, lens, iris, pupil, extraocular muscle movement and eye movements at month 12 and 24. In this outcome measure, data have been reported for right and left eye separately. Rows according to visual status categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.

Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test

Audiological evaluations of participants were recorded and reported using behavior hearing assessment through pure tone audiometry test which includes participants with normal, abnormal, incomplete/inconclusive behavior at month 12 and 24.

Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test

Audiological evaluations of participants were recorded and reported by bone conduction assessment through pure tone audiometry test which included participants with sensorineural hearing loss, conductive hearing loss, mixed hearing loss, neural, and unspecified at month 12 and 24. Rows according to bone conduction categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.

Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test

Audiological evaluations of participants were recorded and reported by air conduction via phones/headphones through pure tone audiometry test which included participants with hearing loss ranged from less than or equal to (<=) 20 decibel hearing loss (DB HL), 21-40 DB HL, 41-70 DB HL, 71-90 DB HL, greater than (>) 90 DB HL or no response, and missing at frequencies ranged from 500 Hertz (Hz) to 8000 Hz at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately. Rows according to air conduction categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.

Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test

Audiological evaluations of participants were recorded and reported by air conduction via soundfield through pure tone audiometry test which included participants with hearing loss ranged from <=20 DB HL, 21-40 DB HL, 41-70 DB HL, 71-90 DB HL, >90 DB HL or no response, and missing at frequencies ranged from 500 Hz to 4000 Hz at month 12 and 24. Rows according to air conduction categories at specified time points are reported in this outcome measure, only when there was a non-zero data for at least 1 reporting arm.

Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test

Audiological evaluations of participants were recorded and reported by tympanometry assessment through immittance audiometry test which included participants with peak pressure signs (+) and (-) at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately.

Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test

Audiological evaluations of participants were recorded and reported by tympanometry assessment through immittance audiometry test which included participants with static acoustic admittance at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately.

Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test

Audiological evaluations of participants were recorded and reported by ipsilateral stapedial reflex through immittance audiometry test which included participants with presence of ipsilateral stapedial reflex at frequencies ranged from 500 Hz to 2000 Hz at month 12 and 24. Ipsilateral stapedial reflex measures are used to assess the neural pathway surrounding the stapedial reflex, which occurs in response to a loud sound (70 to 90 decibel above threshold). In this outcome measure, data have been reported for right and left ear separately.

Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment

Audiological evaluations of participants were recorded and reported by transient evoked emission through otoacoustic emissions assessment which included participants with presence of transient evoked emissions from frequencies 1000 Hz to 4000 Hz at month 12 and 24. In this outcome measure, data have been reported for right and left ear separately.

Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment

Audiological evaluations of participants were recorded and reported by distort product through otoacoustic emissions assessment which included participants with presence of distort product at frequencies ranged from 2000 Hz to 8000 Hz at month 12 and 24. Distortion-product otoacoustic emissions (DPOAEs) are generated in the cochlea in response to two tones of a given frequency and sound pressure level presented in the ear canal. Distort product otoacoustic emissions are an objective indicator of normally functioning cochlea outer hair cells. In this outcome measure, data have been reported for right and left ear separately.

Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths

An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. AEs included both serious and all non-serious AEs.

Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score

The Hammersmith Infant Neurological Examination (HINE) was a standard scoring examination to assess development of cranial nerve; posture; movement; tone; and reflexes and reaction. HINE exam global score is a sum of subset (cranial nerve, posture, movement, tone, reflexes and reactions) scores, ranged from 0 to 78, where higher score represents better outcome. Here, the HINE global scores were reported at month 12 and 24.

Full Information

NCT ID

NCT01720524

First Posted

September 17, 2012

Last Updated

August 12, 2021

Sponsor

Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01720524

Brief Title

A Study To Evaluate Safety And Efficacy Of IV Sildenafil In The Treatment Of Neonates With Persistent Pulmonary Hypertension Of The Newborn

Official Title

A MULTI-CENTRE, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, TWO-ARMED, PARALLEL GROUP STUDY TO EVALUATE EFFICACY AND SAFETY OF IV SILDENAFIL IN THE TREATMENT OF NEONATES WITH PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN (PPHN) OR HYPOXIC RESPIRATORY FAILURE AND AT RISK FOR PPHN, WITH A LONG TERM FOLLOW-UP INVESTIGATION OF DEVELOPMENTAL PROGRESS 12 AND 24 MONTHS AFTER COMPLETION OF STUDY TREATMENT

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

August 5, 2013 (Actual)

Primary Completion Date

October 17, 2018 (Actual)

Study Completion Date

September 28, 2020 (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

This study will evaluate whether IV sildenafil can reduce the time on inhaled nitric oxide treatment and reduce the failure rate of available treatments for persistent pulmonary hypertension of the newborn.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Hypertension, Familial Persistent, of the Newborn

Keywords

persistent pulmonary hypertension, newborn, neonates, iv sildenafil, hypoxic respiratory failure and at risk of persistent pulmonary hypertension of the newborn

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

59 (Actual)

8. Arms, Groups, and Interventions

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

iv placebo of normal saline or 10% dextrose

Arm Title

sildenafil

Arm Type

Experimental

Arm Description

Active study drug

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

IV placebo or 0.9% sodium chloride or 10% dextrose. Infusion rate based on weight.

Intervention Type

Drug

Intervention Name(s)

iv sildenafil

Other Intervention Name(s)

revatio

Intervention Description

loading dose of 0.1 mg/kg over 30 minutes followed by maintenance dose of 0.03 mg/kg/h. To infuse minimum 48 hours and maximum of 14 days.

Primary Outcome Measure Information:

Title

Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure

Description

Time Frame

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)

Title

Treatment Failure Rate

Description

Treatment failure rate was defined as percentage of participants who needed additional treatment targeting PPHN, needed ECMO, or died during the study.

Time Frame

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)

Secondary Outcome Measure Information:

Title

Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation

Description

Time Frame

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)

Title

Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure

Description

Time Frame

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)

Title

Percentage of Participants With Individual Components of Treatment Failure

Description

Time Frame

14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)

Title

Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion

Description

Time Frame

Baseline, Hours 6, 12 and 24 after start of infusion

Title

Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion

Description

Time Frame

Baseline, Hours 6, 12 and 24 after start of infusion

Title

Change From Baseline in Ratio of Partial Pressure of Oxygen in Arterial Blood to Fraction of Inspired Oxygen (P/F) at Hours 6, 12 and 24

Description

Time Frame

Baseline, Hours 6, 12 and 24 after start of infusion

Title

Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite

Description

Cmax was obtained for Sildenafil and its major metabolite UK-103,320.

Time Frame

Loading dose, Day 1: prior to the start of infusion, 5, 30 minutes after end of loading infusion; Maintenance dose: 48 to 72, 96 to 120 hours during infusion and immediately prior to end of maintenance infusion (up to maximum on Day 14)

Title

Total Plasma Clearance (CL) of Sildenafil and Its Metabolite

Description

CL is volume of the body fluid/ plasma from which the drug or the metabolite is completely removed per unit time. CL was obtained for Sildenafil and its major metabolite UK-103,320.

Time Frame

Loading dose: prior to the start of infusion, 5, 30 minutes after end of loading infusion on Day 1; Maintenance dose: between 48 to 72, 96 to 120 hours during infusion and immediately prior to end of infusion on Day 1

Title

Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite

Description

Time Frame

Title

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Description

Time Frame

Baseline up to 31 days after end of study drug infusion (up to 45 days)

Title

Number of Treatment-Emergent Adverse Events (AEs) According to Severity

Description

Time Frame

Baseline up to 31 days after end of study drug infusion (up to 45 days)

Title

Number of Participants With Laboratory Abnormalities

Description

Time Frame

Up to 14 days from initiation of study drug infusion

Title

Part B: Composite Scores of Cognitive, Language, and Motor Developmental Progress of Participants as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Composite Scores of Social-Emotional and Adaptive Behavior Questionnaire as Assessed by Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)

Description

Time Frame

Month 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

Title

Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths

Description

Time Frame

up to 24 months after end of study treatment in Part A (maximum up to 26 months)

Title

Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score

Description

Time Frame

Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

0 Days

Maximum Age & Unit of Time

4 Days

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Neonates with persistent pulmonary hypertension of the newborn Age <=96 hours and >=34 weeks gestational age Oxygenation Index >15 and <60 Concurrent treatment with inhaled nitric oxide and >=50% oxygen Exclusion Criteria: Prior or immediate need for extracorporeal membrane oxygenation or cardiopulmonary resuscitation Expected duration of mechanical ventilation <48 hours Profound hypoxemia Life-threatening or lethal congenital anomaly

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

Arkansas Children's Hospital

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72202

Country

United States

Facility Name

University of California Davis Medical Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

University of California Davis

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

University of California Davis Medical Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95825

Country

United States

Facility Name

Children´s National Medical Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20010

Country

United States

Facility Name

Indiana University Health Methodist Hospital

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Riley Hospital for Children at IU Health

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Sydney and Lois Eskenazi Hospital

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Children's Mercy Hospitals & Clinics

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64108

Country

United States

Facility Name

Duke University Medical Center (DUMC)

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Fairview Hospital

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44111

Country

United States

Facility Name

Cleveland Clinic

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

OU Follow-Up Program, PREMIEr Clinic, Children's Hospital

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

OU Neonatal Intensive Care Unit at Children's Hospital

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

The University of Oklahoma Health Sciences Center

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

Henry Zarrow Neonatal Intensive Care Unit, Children's Hospital at Saint Francis

City

Tulsa

State/Province

Oklahoma

ZIP/Postal Code

74136

Country

United States

Facility Name

Warren Cancer Research Foundation

City

Tulsa

State/Province

Oklahoma

ZIP/Postal Code

74136

Country

United States

Facility Name

Vanderbilt Children's Hospital

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Seattle Children's Research Institute

City

Seattle

State/Province

Washington

ZIP/Postal Code

98101

Country

United States

Facility Name

Seattle Childrens Hospital

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105

Country

United States

Facility Name

Universitair Ziekenhuis Antwerpen

City

Edegem

ZIP/Postal Code

2650

Country

Belgium

Facility Name

UZ Gent

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

CHUL du CHU de Quebec

City

Quebec

ZIP/Postal Code

G1V 4G2

Country

Canada

Facility Name

Aarhus Universitetshospital, Skejby

City

Aarhus N

ZIP/Postal Code

8200

Country

Denmark

Facility Name

Neonatalklinikken Rigshospitalet, 5024

City

Copenhagen Ø

ZIP/Postal Code

2100

Country

Denmark

Facility Name

Centre Hospitalier et Regional de Lille - Hopital Jeanne de Flandre

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Centre Hospitalier et Régional de Lille,

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Hôpital de la Conception Assistance Publique-Hôpitaux de Marseille

City

Marseille

ZIP/Postal Code

13385

Country

France

Facility Name

CHU Robert Debré

City

Paris

ZIP/Postal Code

75019

Country

France

Facility Name

Hopital NECKER - Enfants Malades

City

Paris

ZIP/Postal Code

75743

Country

France

Facility Name

University Hospital of Leipzig

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Neonatologia Fondazione IRCCS Policlinico San Matteo

City

Pavia

ZIP/Postal Code

27100

Country

Italy

Facility Name

Radboud University Nijmegen Medical Centre

City

Nijmegen

ZIP/Postal Code

6525 GA

Country

Netherlands

Facility Name

Erasmus MC, Sophia Children's hospital

City

Rotterdam

ZIP/Postal Code

3015 CN

Country

Netherlands

Facility Name

Haukeland University Hospital

City

Bergen

State/Province

Haukeland

ZIP/Postal Code

5000

Country

Norway

Facility Name

Hospital Sant Joan de Deu

City

Esplugues de Llobregat

State/Province

Barcelona / Spain

ZIP/Postal Code

08950

Country

Spain

Facility Name

Hospital General Universitario Gregorio Marañon

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Karolinska University Hospital

City

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

Facility Name

St. Michael's Hospital

City

Bristol

ZIP/Postal Code

BS2 8EG

Country

United Kingdom

Facility Name

Leicester Royal Infirmary

City

Leicester

ZIP/Postal Code

LE1 5WW

Country

United Kingdom

Facility Name

Glenfield Hospital, University Hospitals of Leicester NHS Trust

City

Leicester

ZIP/Postal Code

LE3 9QP

Country

United Kingdom

Facility Name

Great Ormond Street Hospital NHS Foundation Trust

City

London

ZIP/Postal Code

WC1N 3JH

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

IPD Sharing URL

https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Citations:

PubMed Identifier

34052232

Citation

Pierce CM, Zhang MH, Jonsson B, Iorga D, Cheruvu N, Balagtas CC, Steinhorn RH. Efficacy and Safety of IV Sildenafil in the Treatment of Newborn Infants with, or at Risk of, Persistent Pulmonary Hypertension of the Newborn (PPHN): A Multicenter, Randomized, Placebo-Controlled Trial. J Pediatr. 2021 Oct;237:154-161.e3. doi: 10.1016/j.jpeds.2021.05.051. Epub 2021 May 27.

Results Reference

derived

Links:

URL

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A1481316&StudyName=A%20Study%20To%20Evaluate%20Safety%20And%20Efficacy%20Of%20IV%20Sildenafil%20In%20The%20Treatment%20Of%20Neonates%20With%20Persistent%20Pulmonary%20Hypertension%20Of%20The%20

Description

To obtain contact information for a study center near you, click here.

Learn more about this trial

A Study To Evaluate Safety And Efficacy Of IV Sildenafil In The Treatment Of Neonates With Persistent Pulmonary Hypertension Of The Newborn

We'll reach out to this number within 24 hrs