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

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ClinicalTrials.gov Identifier: NCT01720524
Recruitment Status : Active, not recruiting
First Posted : November 2, 2012
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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
Actual Study Start Date : August 5, 2013
Actual Primary Completion Date : November 13, 2018
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Time on inhaled nitric oxide treatment after initiation of iv study drug [ Time Frame: Day 14 or hospital discharge ]
  2. Treatment failure rate, defined as need for additional treatment targeting persistent pulmonary hypertension of the newborn. [ Time Frame: day 14 or hospital discharge ]

Secondary Outcome Measures :
  1. Time to final weaning of mechanical ventilation for persistent pulmonary hypertension of the newborn [ Time Frame: Day 14 or hospital discharge ]
  2. Time from initiation of study drug to treatment failure [ Time Frame: Day 14 or hospital discharge ]
  3. Change in oxygenation parameters at 6, 12, and 24 hours from baseline [ Time Frame: Day 14 or hospital discharge ]
  4. Sildenafil plasma concentrations and corresponding PK parameters [ Time Frame: Day 14 or hospital discharge ]
  5. Safety parameters: incidence and severity of adverse events and abnormal laboratory parameters [ Time Frame: Day 14 or hospital discharge ]

Other Outcome Measures:
  1. 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 ]
    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

  2. Safety, assessed by adverse events and survival [ Time Frame: At 12 and 24 months after completion of study treatment ]
  3. 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 ]
    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

  4. 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. ]
    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.

  5. Audiological status of subjects as assessed by Physiological and Behavioral tests [ Time Frame: Months 12 and 24 after completion of study treatment ]
    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)



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Ages Eligible for Study:   up to 4 Days   (Child)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01720524


  Hide Study Locations
Locations
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, California
University of California Davis Medical Center
Sacramento, California, United States, 95817
University of California Davis
Sacramento, California, United States, 95817
United States, District of Columbia
Children´s National Medical Center
Washington, District of Columbia, United States, 20010
United States, Georgia
Emory University Hospital Midtown
Atlanta, Georgia, United States, 30308
Emory Developmental Progress Clinic
Atlanta, Georgia, United States, 30322
Emory Eye Clinic
Atlanta, Georgia, United States, 30322
Children's Healthcare of Atlanta at North Driud Hills
Atlanta, Georgia, United States, 30324
United States, Indiana
Indiana University Health Methodist Hospital
Indianapolis, Indiana, United States, 46202
Riley Hospital for Children at IU Health
Indianapolis, Indiana, United States, 46202
Sydney and Lois Eskenazi Hospital
Indianapolis, Indiana, United States, 46202
United States, Kentucky
NICU Graduate Clinic
Lexington, Kentucky, United States, 40504
Kentucky Children's Hospital
Lexington, Kentucky, United States, 40536
United States, Missouri
Children's Mercy Hospitals & Clinics
Kansas City, Missouri, United States, 64108
United States, New Jersey
Bristol Myers Squibb Children's Hospital at Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08901
Rutgers-Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08901
United States, North Carolina
Duke University Medical Center (DUMC)
Durham, North Carolina, United States, 27710
United States, Ohio
Fairview Hospital
Cleveland, Ohio, United States, 44111
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Oklahoma
OU Follow-Up Program, PREMIEr Clinic, Children's Hospital
Oklahoma City, Oklahoma, United States, 73104
OU Neonatal Intensive Care Unit at Children's Hospital
Oklahoma City, Oklahoma, United States, 73104
The University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Henry Zarrow Neonatal Intensive Care Unit, Children's Hospital at Saint Francis
Tulsa, Oklahoma, United States, 74136
Warren Cancer Research Foundation
Tulsa, Oklahoma, United States, 74136
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232
United States, Washington
Seattle Children's Research Institute
Seattle, Washington, United States, 98101
Seattle Childrens Hospital
Seattle, Washington, United States, 98105
Belgium
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, 2650
UZ Gent
Gent, Belgium, 9000
Canada
CHUL du CHU de Quebec
Quebec, Canada, G1V 4G2
Denmark
Aarhus Universitetshospital, Skejby
Aarhus N, Denmark, 8200
Neonatalklinikken Rigshospitalet, 5024
Copenhagen Ø, Denmark, 2100
France
Centre Hospitalier et Regional de Lille - Hopital Jeanne de Flandre
Lille, France, 59037
Centre Hospitalier et Régional de Lille,
Lille, France, 59037
Hôpital de la Conception Assistance Publique-Hôpitaux de Marseille
Marseille, France, 13385
CHU Robert Debré
Paris, France, 75019
Hopital NECKER - Enfants Malades
Paris, France, 75743
Germany
Universitaetsklinikum Heidelberg - Zentrum für Kinder- und Jugendmedizin
Heidelberg, Germany, 69120
University Hospital of Leipzig
Leipzig, Germany, 04103
Universitätsklinikum Mannheim
Mannheim, Germany, 68167
Italy
Neonatologia Fondazione IRCCS Policlinico San Matteo
Pavia, Italy, 27100
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6525 GA
Erasmus MC, Sophia Children's hospital
Rotterdam, Netherlands, 3015 CN
Norway
Haukeland University Hospital
Bergen, Haukeland, Norway, 5000
Spain
Hospital Sant Joan de Deu
Esplugues de Llobregat, Barcelona / Spain, Spain, 08950
Hospital General Universitario Gregorio Marañon
Madrid, Spain, 28007
Sweden
Karolinska University Hospital Solna
Stockholm, Sweden, 171 76
United Kingdom
St. Michael's Hospital
Bristol, United Kingdom, BS2 8EG
Leicester Royal Infirmary
Leicester, United Kingdom, LE1 5WW
Glenfield Hospital, University Hospitals of Leicester NHS Trust
Leicester, United Kingdom, LE3 9QP
Great Ormond Street Hospital NHS Foundation Trust
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01720524     History of Changes
Other Study ID Numbers: A1481316
2012-002619-24 ( EudraCT Number )
First Posted: November 2, 2012    Key Record Dates
Last Update Posted: January 15, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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