Clinical trial NCT01670136: Pharmacokinetics of Sildenafil in Premature Infants
Official title: Pharmacokinetics of Sildenafil in Premature Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Persistent Pulmonary Hypertension of the Newborn
Keywords: sildenafil
preterm infants
persistent pulmonary hypertension of the newborn
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Duke University
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: The Emmes Company, LLC
First posted: 2012-08-21
Enrollment: 34
Sex: ALL
Maximum age (years): 364
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Area under the plasma concentration versus time curve 0-24 hours for sildenafil
timeFrame: 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
measure: Peak plasma concentration of sildenafil
timeFrame: 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
measure: Clearance of sildenafil
timeFrame: 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
measure: Volume of distribution at steady state
timeFrame: 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
measure: Half life of sildenafil
timeFrame: 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 outcomes:
measure: Number of subjects with adverse events as a measure of safety and tolerability.
timeFrame: 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
measure: Correlation between serum and dried blood spot samples
timeFrame: 1-7 days
measure: Evaluate P450 single nucleotide polymorphisms (SNPs)
timeFrame: 2-7 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Indianapolis
country: United States
facility: Riley Hospital
state: Indiana
city: Louisville
country: United States
facility: Kosair Pediatric Research Unit
state: Kentucky
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Brooklyn
country: United States
facility: Kings County Hospital Center/SUNY Downstate Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: University of North Carolina
name: Matthew M Laughon, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jackson W, Gonzalez D, Smith PB, Ambalavanan N, Atz AM, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Ahlfeld SK, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP, Laughon MM; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Safety of sildenafil in extremely premature infants: a phase I trial. J Perinatol. 2022 Jan;42(1):31-36. doi: 10.1038/s41372-021-01261-w. Epub 2021 Nov 5.