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 May 2016 by Pfizer
Information provided by (Responsible Party):
ClinicalTrials.gov Identifier:
First received: September 17, 2012
Last updated: May 12, 2016
Last verified: May 2016
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
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


Ages Eligible for Study:   up to 4 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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

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

  Show 53 Study Locations
Sponsors and Collaborators
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: May 12, 2016
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on May 26, 2016