Persistent Pulmonary Hypertension of the Newborn
Conditions
Keywords
sildenafil, preterm infants, persistent pulmonary hypertension of the newborn
Brief summary
The purpose of this study is to learn more about the safety and dosing of sildenafil in infants.
Detailed description
Pharmacokinetics and safety of sildenafil will be studied in preterm infants who are receiving sildenafil per standard of care or 1 dose prescribed for the study.
Interventions
DRUG1 dose of sildenafil
A single IV dose of sildenafil will be administered over 90 minutes with no greater than a 15-minute flush. Final dose to be determined based on at least the first 4 participants enrolled in Cohort 1; final dose expected to be a single dose between 0.25 and 0.5 mg/kg.
Sponsors
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The Emmes Company, LLC
University of North Carolina, Chapel Hill
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 364 Days
Healthy volunteers
No
Inclusion criteria
Cohort 1: * Gestational age 28 weeks or less receiving sildenafil as standard of care \< 365 postnatal days Cohort 2: * Gestational age 28 weeks or less * 7-28 postnatal days of age * Mechanical ventilation or nasal continuous positive airway pressure (NCPAP) or high-flow nasal cannula * Intravenous line in place
Exclusion criteria
Cohort 1: * Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study Cohort 2: * Previous exposure to sildenafil within 7 days prior to enrollment * Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study * History of allergic reactions to sildenafil * AST \> ULN or ALT \> 3x ULN * Currently on a vasopressor for hypotension * Known sickle cell disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clearance of sildenafil | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose |
| Area under the plasma concentration versus time curve 0-24 hours for sildenafil | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose |
| Peak plasma concentration of sildenafil | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose |
| Volume of distribution at steady state | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose |
| Half life of sildenafil | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose |
Secondary
| Measure | Time frame |
|---|---|
| Correlation between serum and dried blood spot samples | 1-7 days |
| Evaluate P450 single nucleotide polymorphisms (SNPs) | 2-7 days |
| Number of subjects with adverse events as a measure of safety and tolerability. | From the time of the first dose to 3 days after the last dose; serious adverse events will be collected from the first dose of sildenafil to 7 days after the last dose of sildenafil |
Countries
United States
Outcome results
None listed