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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01720524
First received: September 17, 2012
Last updated: August 23, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Pulmonary Hypertension, Familial Persistent, of the Newborn
Drug: placebo
Drug: iv sildenafil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Time on inhaled nitric oxide treatment after initiation of iv study drug [ Time Frame: Day 14 or hospital discharge ] [ Designated as safety issue: No ]
  • Treatment failure rate, defined as need for additional treatment targeting persistent pulmonary hypertension of the newborn. [ Time Frame: day 14 or hospital discharge ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to final weaning of mechanical ventilation for persistent pulmonary hypertension of the newborn [ Time Frame: Day 14 or hospital discharge ] [ Designated as safety issue: No ]
  • Time from initiation of study drug to treatment failure [ Time Frame: Day 14 or hospital discharge ] [ Designated as safety issue: No ]
  • Change in oxygenation parameters at 6, 12, and 24 hours from baseline [ Time Frame: Day 14 or hospital discharge ] [ Designated as safety issue: No ]
  • Sildenafil plasma concentrations and corresponding PK parameters [ Time Frame: Day 14 or hospital discharge ] [ Designated as safety issue: No ]
  • Safety parameters: incidence and severity of adverse events and abnormal laboratory parameters [ Time Frame: Day 14 or hospital discharge ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Developmental progress of subjects as assessed by Bayley Scales of Infant Development and Behavior Questionnaire [ Time Frame: Months 12 and 24 after completion of study treatment ] [ Designated as safety issue: No ]
    Bayley Scales of Infant Development is a standard series of measurements to assess motor (fine and gross), language (expressive and comprehensive), and cognitive development of infants and toddlers, ages 0-3 years. Bayley Questionnaire for Parent/Caregiver is used to assess Social-Emotional and Adaptive Behavior development of toddlers, ages 0-3 years

  • Safety, assessed by adverse events and survival [ Time Frame: At 12 and 24 months after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Neurological progress of subjects as assessed by the Neurology Optimality Score, also known as the Hammersmith Infant Neurological Examination [ Time Frame: Months 12 and 24 after end of study treatment ] [ Designated as safety issue: No ]
    The Hammersmith Infant Neurological Examination is a standard scoring examination to assess development of cranial nerve, posture, movement, tone, reflexes and reaction, and global neurological status, ages 0-18 months

  • Visual status of subjects as assessed by eye examinations of the anterior and posterior segments [ Time Frame: Months 12 and 24 after completion of study treatment. ] [ Designated as safety issue: No ]
    Standard age-appropriate ophthalmological examinations will be used to assess general eye status, visual acuity (with Teller cards and fix and follow), pupil response and fundus examination, and refraction measured.

  • Audiological status of subjects as assessed by Physiological and Behavioral tests [ Time Frame: Months 12 and 24 after completion of study treatment ] [ Designated as safety issue: No ]
    Standard developmentally appropriate audiological examinations suited to the individual subject will be used to assess auditory system function (physical tests: tympanometry, acoustic reflex, otoacoustic emissions) and hearing sensitivity (behavioral test: visual reinforcement audiometry)


Estimated Enrollment: 64
Study Start Date: August 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
iv placebo of normal saline or 10% dextrose
Drug: placebo
IV placebo or 0.9% sodium chloride or 10% dextrose. Infusion rate based on weight.
Experimental: sildenafil
Active study drug
Drug: iv sildenafil
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.
Other Name: revatio

  Eligibility

Ages Eligible for Study:   up to 4 Days   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01720524

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

  Hide Study Locations
Locations
United States, Alabama
University Hospital Woman and Infants Center Recruiting
Birmingham, Alabama, United States, 35249
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
United States, California
University of California, Davis Children's Hospital Recruiting
Sacramento, California, United States, 95817
United States, District of Columbia
Childrens National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
United States, Indiana
Indiana University Health Methodist Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Riley Hospital for Children at IU Health Recruiting
Indianapolis, Indiana, United States, 46202
Sydney and Lois Eskenazi Hospital Recruiting
Indianapolis, Indiana, United States, 46202
United States, Missouri
Children's Mercy Hospitals & Clinics Recruiting
Kansas City, Missouri, United States, 64108
United States, North Carolina
Duke University Medical Center (DUMC) Terminated
Durham, North Carolina, United States, 27710
United States, Oklahoma
OU Follow-Up Program, PREMIEr Clinic, Children's Hospital Recruiting
Oklahoma City, Oklahoma, United States, 73104
OU Neonatal Intensive Care Unit at Children's Hospital Recruiting
Oklahoma City, Oklahoma, United States, 73104
The University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Henry Zarrow Neonatal Intensive Care Unit, Children's Hospital at Saint Francis Terminated
Tulsa, Oklahoma, United States, 74136
Warren Cancer Research Foundation Terminated
Tulsa, Oklahoma, United States, 74136
United States, Tennessee
Vanderbilt Children's Hospital Recruiting
Nashville, Tennessee, United States, 37232
United States, Washington
Seattle Children's Research Institute Recruiting
Seattle, Washington, United States, 98101
Seattle Childrens Hospital Recruiting
Seattle, Washington, United States, 98105
Belgium
Universitair Ziekenhuis Antwerpen Active, not recruiting
Edegem, Belgium, 2650
UZ Gent Recruiting
Gent, Belgium, 9000
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
McGill University Health Centre Glen Site Montreal Children's Hospital Recruiting
Montreal, Quebec, Canada, H4A 3J1
Canada
CHUL du CHU de Quebec Recruiting
Quebec, Canada, G1V 4G2
Denmark
Aarhus Universitetshospital, Skejby Recruiting
Aarhus N, Denmark, 8200
Neonatalklinikken Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
France
Centre Hospitalier et Regional de Lille - Hopital Jeanne de Flandre Recruiting
Lille, France, 59037
Centre Hospitalier et Régional de Lille, Recruiting
Lille, France, 59037
Hôpital de la Conception Assistance Publique-Hôpitaux de Marseille Recruiting
Marseille, France, 13385
CHU Robert Debré Terminated
Paris, France, 75019
Hopital NECKER - Enfants Malades Recruiting
Paris, France, 75743
Germany
Universitaetsklinikum Heidelberg - Zentrum für Kinder- und Jugendmedizin Recruiting
Heidelberg, Germany, 69120
Universitaetsklinikum Leipzig Recruiting
Leipzig, Germany, 04103
Universitätsklinikum Mannheim Recruiting
Mannheim, Germany, 68167
Italy
Neonatologia e Terapia Intensiva Neonatale Azienda Ospedaliera Spedali Civili di Brescia Recruiting
Brescia, NAP, Italy, 25123
A.O. Spedali Civili Recruiting
Brescia, Italy, 25123
Neonatologia Fondazione IRCCS Policlinico San Matteo Recruiting
Pavia, Italy, 27100
Netherlands
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands, 6525 GA
Erasmus MC, Sophia Children's hospital Recruiting
Rotterdam, Netherlands, 3015 GN
Norway
Haukeland University Hospital Recruiting
Bergen, Norway, 5021
Spain
Hospital San Joan de Deu Recruiting
Esplugues de Llobregat, Barcelona / Spain, Spain, 08950
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Hospital General Universitario Gregorio Marañon Recruiting
Madrid, Spain, 28007
Hospital Universitari i Politecnic La Fe Recruiting
Valencia, Spain, 46026
Sweden
Karolinska University Hospital and Institute Recruiting
Stockholm, Sweden, 171 76
United Kingdom
St. Michael's Hospital Recruiting
Bristol, United Kingdom, BS2 8EG
Leeds Teaching Hospitals NHS Trust Recruiting
Leeds, United Kingdom, LS13EX
Leicester Royal Infirmary Recruiting
Leicester, United Kingdom, LE1 5WW
Glenfield Hospital, University Hospitals of Leicester NHS Trust Recruiting
Leicester, United Kingdom, LE3 9QP
Great Ormond Street Hospital NHS Foundation Trust Recruiting
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01720524     History of Changes
Other Study ID Numbers: A1481316  2012-002619-24 
Study First Received: September 17, 2012
Last Updated: August 23, 2016
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration

Keywords provided by Pfizer:
persistent pulmonary hypertension
newborn
neonates
iv sildenafil
hypoxic respiratory failure and at risk of persistent pulmonary hypertension of the newborn

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Respiratory Insufficiency
Persistent Fetal Circulation Syndrome
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Newborn, Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on August 28, 2016