Phase 3 N=59 Randomized Double-blind Treatment

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

Pulmonary Hypertension, Familial Persistent, of the Newborn

Bottom Line

View on ClinicalTrials.gov: NCT01720524 ↗

Enrolled (actual)

Serious AEs

21.4%

Results posted

Mar 2020

Primary outcome: Primary: Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure — 4.1; 4.1 days — p=0.9850

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: placebo (Drug); iv sildenafil (Drug)
Age: Pediatric · 0+ yrs
Sex: All
Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Primary completion: Oct 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Time on Inhaled Nitric Oxide (iNO) Treatment After Initiation of Intravenous (IV) Study Drug For Participants Without Treatment Failure	4.1; 4.1	0.9850
PRIMARY Treatment Failure Rate	27.6; 20.0	0.4935
SECONDARY Time From Initiation of Intravenous (IV) Study Drug to Final Weaning of Mechanical Ventilation	8.3; 7.3	0.9885
SECONDARY Time From Initiation of Intravenous (IV) Study Drug to First Treatment Failure	NA; NA	0.4910
SECONDARY Percentage of Participants With Individual Components of Treatment Failure	13.8; 10.0; 10.3; 10.0; 6.9; 0.0	0.7065
SECONDARY Change From Baseline in Oxygenation Index (OI) at Hours 6, 12 and 24 Post-Infusion	-4.2; -8.0; -4.1; -8.2; -11.6; -9.5	0.4984
SECONDARY Change From Baseline in Differential Saturation at Hours 6, 12 and 24 Post-Infusion	1.5; 0.8; -1.2; 6.7; 1.2; 9.3	0.7686
SECONDARY 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	45.3; 8.1; 43.4; 16.9; 94.6; 14.7	0.0829
SECONDARY Maximum Plasma Concentration (Cmax) of Sildenafil and Its Metabolite	52.64; 1.04; 78.12; 21.65	—
SECONDARY Total Plasma Clearance (CL) of Sildenafil and Its Metabolite	1.78; 5.05	—
SECONDARY Central Volume of Distribution (Vc) of Sildenafil and Its Metabolite	8.76; 15.96	—
SECONDARY Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	22; 19; 7; 2	—
SECONDARY Number of Treatment-Emergent Adverse Events (AEs) According to Severity	49; 42; 29; 24; 12; 17	—
SECONDARY Number of Participants With Laboratory Abnormalities	27; 22	—
SECONDARY 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)	97.5; 94.5; 97.4; 97.3; 99.5; 94.7	—
SECONDARY 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)	104.5; 112.5; 91.6; 98.3	—
SECONDARY Part B: Number of Participants With Eye Movement Disorders as Assessed by Eye Examination	0; 1; 0; 1; 1; 0	—
SECONDARY Part B: Visual Acuity of Verbal Participants as Assessed by Ophthalmological Assessment	2; 1; 0; 2; 1; 0	—
SECONDARY Part B: Visual Acuity of Non-Verbal Participants as Assessed by Ophthalmological Assessment	15; 13; 0; 1; 1; 0	—
SECONDARY Part B: Visual Acuity of Verbal Participants as Assessed by LogMAR Through Visual Acuity Chart	0.45; 0.57; 0.47; 0.57; 0.20; 0.28	—
SECONDARY Part B: Visual Status of Participants With Abnormality as Assessed by Eye Examination of the Anterior and Posterior Segments	0; 1; 0; 1; 1; 0	—
SECONDARY Part B: Audiological Status of Participants as Assessed by Behavior Hearing Assessment Through Pure Tone Audiometry Test	11; 8; 1; 4; 4; 0	—
SECONDARY Part B: Audiological Status of Participants as Assessed by Bone Conduction Through Pure Tone Audiometry Test	0; 1; 1; 1; 1	—
SECONDARY Part B: Audiological Status of Participants as Assessed by Air Conduction Via Phones/Headphones Through Pure Tone Audiometry Test	3; 4; 2; 1; 4; 5	—
SECONDARY Part B: Audiological Status of Participants as Assessed by Air Conduction Via Soundfield Through Pure Tone Audiometry Test	6; 2; 5; 6; 1; 0	—
SECONDARY Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Peak Pressure) Through Immittance Audiometry Test	51.89; 27.33; 5.07; 73.75; 44.00; 33.50	—
SECONDARY Part B: Audiological Status of Participants as Assessed by Tympanometry Assessment (Static Acoustic Admittance) Through Immittance Audiometry Test	0.241; 0.403; 0.364; 0.330; 0.273; 0.400	—
SECONDARY Part B: Audiological Status of Participants as Assessed by Ipsilateral Stapedial Reflex Through Immittance Audiometry Test	5; 1; 6; 1; 5; 1	—
SECONDARY Part B: Audiological Status of Participants as Assessed by Transient Evoked Emission Through Otoacoustic Emissions Assessment	3; 2; 2; 1; 3; 2	—
SECONDARY Part B: Audiological Status of Participants as Assessed by Distort Product Through Otoacoustic Emissions Assessment	4; 4; 5; 3; 5; 4	—
SECONDARY Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Deaths	17; 17; 9; 6; 0; 2	—
SECONDARY Part B: Neurological Progress of Participants as Assessed by the Neurology Optimality Score	69.9; 75.6; 65.6; 76.5	—

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 =34 weeks gestational age
Oxygenation Index >15 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01720524). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.