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Pharmacokinetics of Sildenafil in Premature Infants

Primary Purpose

Persistent Pulmonary Hypertension of the Newborn

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
1 dose of sildenafil
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Persistent Pulmonary Hypertension of the Newborn focused on measuring sildenafil, preterm infants, persistent pulmonary hypertension of the newborn

Eligibility Criteria

undefined - 364 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • Riley Hospital
  • Kosair Pediatric Research Unit
  • Albany Medical Center
  • Kings County Hospital Center/SUNY Downstate Medical Center
  • University of North Carolina
  • Duke University
  • Cincinnati Children's Hospital Medical Center
  • Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Other

Arm Label

sildenafil, standard of care

sildenafil administered for study

Arm Description

Infants receiving sildenafil as standard of care

1 dose of sildenafil administered for study

Outcomes

Primary Outcome Measures

Area under the plasma concentration versus time curve 0-24 hours for sildenafil
Peak plasma concentration of sildenafil
Clearance of sildenafil
Volume of distribution at steady state
Half life of sildenafil

Secondary Outcome Measures

Number of subjects with adverse events as a measure of safety and tolerability.
Correlation between serum and dried blood spot samples
Evaluate P450 single nucleotide polymorphisms (SNPs)

Full Information

First Posted
August 17, 2012
Last Updated
November 1, 2016
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01670136
Brief Title
Pharmacokinetics of Sildenafil in Premature Infants
Official Title
Pharmacokinetics of Sildenafil in Premature Infants
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Persistent Pulmonary Hypertension of the Newborn
Keywords
sildenafil, preterm infants, persistent pulmonary hypertension of the newborn

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
sildenafil, standard of care
Arm Type
No Intervention
Arm Description
Infants receiving sildenafil as standard of care
Arm Title
sildenafil administered for study
Arm Type
Other
Arm Description
1 dose of sildenafil administered for study
Intervention Type
Drug
Intervention Name(s)
1 dose of sildenafil
Other Intervention Name(s)
Revatio, Viagra
Intervention Description
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.
Primary Outcome Measure Information:
Title
Area under the plasma concentration versus time curve 0-24 hours for sildenafil
Time Frame
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
Title
Peak plasma concentration of sildenafil
Time Frame
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
Title
Clearance of sildenafil
Time Frame
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
Title
Volume of distribution at steady state
Time Frame
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
Title
Half life of sildenafil
Time Frame
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 Outcome Measure Information:
Title
Number of subjects with adverse events as a measure of safety and tolerability.
Time Frame
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
Title
Correlation between serum and dried blood spot samples
Time Frame
1-7 days
Title
Evaluate P450 single nucleotide polymorphisms (SNPs)
Time Frame
2-7 days

10. Eligibility

Sex
All
Maximum Age & Unit of Time
364 Days
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew M Laughon, MD, MPH
Organizational Affiliation
University of North Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249-7335
Country
United States
Facility Name
Riley Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Kosair Pediatric Research Unit
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Albany Medical Center
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Kings County Hospital Center/SUNY Downstate Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34741102
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.
Results Reference
derived

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Pharmacokinetics of Sildenafil in Premature Infants

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