Clinical trial NCT01720524: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-11-02
Enrollment: 59
Sex: ALL
Minimum age (years): 0
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure
timeFrame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
measure: Treatment Failure Rate
timeFrame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
Secondary outcomes:
measure: Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation
timeFrame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
measure: Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure
timeFrame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
measure: Percentage of Participants With Individual Components of Treatment Failure
timeFrame: 14 days from the initiation of IV study drug or hospital discharge, whichever occurs first (maximum of 14 days)
measure: Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion
timeFrame: Baseline, Hours 6, 12 and 24 after start of infusion
measure: Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion
timeFrame: Baseline, Hours 6, 12 and 24 after start of infusion
measure: 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
timeFrame: Baseline, Hours 6, 12 and 24 after start of infusion
measure: Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite
timeFrame: 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)
measure: Total Plasma Clearance (CL) of Sildenafil and Its Metabolite
timeFrame: 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
measure: Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite
timeFrame: 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
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 31 days after end of study drug infusion (up to 45 days)
measure: Number of Treatment-Emergent Adverse Events (AEs) According to Severity
timeFrame: Baseline up to 31 days after end of study drug infusion (up to 45 days)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Up to 14 days from initiation of study drug infusion
measure: 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)
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: 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)
timeFrame: Month 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
measure: Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths
timeFrame: up to 24 months after end of study treatment in Part A (maximum up to 26 months)
measure: Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score
timeFrame: Month 12 and 24 after end of study treatment in Part A (Day 1 to 14)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Washington
country: United States
facility: Children´s National Medical Center
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University Health Methodist Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children at IU Health
state: Indiana
city: Indianapolis
country: United States
facility: Sydney and Lois Eskenazi Hospital
state: Indiana
city: Kansas City
country: United States
facility: Children's Mercy Hospitals & Clinics
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center (DUMC)
state: North Carolina
city: Cleveland
country: United States
facility: Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: OU Follow-Up Program, PREMIEr Clinic, Children's Hospital
state: Oklahoma
city: Oklahoma City
country: United States
facility: OU Neonatal Intensive Care Unit at Children's Hospital
state: Oklahoma
city: Oklahoma City
country: United States
facility: The University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Henry Zarrow Neonatal Intensive Care Unit, Children's Hospital at Saint Francis
state: Oklahoma
city: Tulsa
country: United States
facility: Warren Cancer Research Foundation
state: Oklahoma
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Seattle
country: United States
facility: Seattle Children's Research Institute
state: Washington
city: Seattle
country: United States
facility: Seattle Childrens Hospital
state: Washington
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Quebec
country: Canada
facility: CHUL du CHU de Quebec
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Skejby
city: Copenhagen Ø
country: Denmark
facility: Neonatalklinikken Rigshospitalet, 5024
city: Lille
country: France
facility: Centre Hospitalier et Regional de Lille - Hopital Jeanne de Flandre
city: Lille
country: France
facility: Centre Hospitalier et Régional de Lille,
city: Marseille
country: France
facility: Hôpital de la Conception Assistance Publique-Hôpitaux de Marseille
city: Paris
country: France
facility: CHU Robert Debré
city: Paris
country: France
facility: Hopital NECKER - Enfants Malades
city: Leipzig
country: Germany
facility: University Hospital of Leipzig
city: Pavia
country: Italy
facility: Neonatologia Fondazione IRCCS Policlinico San Matteo
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
city: Rotterdam
country: Netherlands
facility: Erasmus MC, Sophia Children's hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
state: Haukeland
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Barcelona / Spain
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Bristol
country: United Kingdom
facility: St. Michael's Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Leicester
country: United Kingdom
facility: Glenfield Hospital, University Hospitals of Leicester NHS Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.