Persistent Pulmonary Hypertension of the NewbornPhase 1NCT01670136
Pharmacokinetics of Sildenafil in Premature Infants
A Phase 1 study testing 1 dose of sildenafil in people with Persistent Pulmonary Hypertension of the Newborn, run by University of North Carolina, Chapel Hill at 9 sites in United States.
Trial summary
The purpose of this study is to learn more about the safety and dosing of sildenafil in infants. Read more about this study
- Who is it for?
- Ages Up to 364 days
- Conditions the study is for
- Persistent Pulmonary Hypertension of the Newborn
- What is being tested?
- 1 dose of sildenafil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 9 sitesUnited States
- Study dates
- Feb 2013to Jul 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 364 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- AST > ULN or ALT > 3x ULN
- Currently on a vasopressor for hypotension
- Known sickle cell disease
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Albany Medical Center
Albany, New York, 12208
University of Alabama at Birmingham
Birmingham, Alabama, 35249-7335
Kings County Hospital Center/SUNY Downstate Medical Center
Brooklyn, New York, 11203
University of North Carolina
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Duke University
Durham, North Carolina, 27705
Riley Hospital
Indianapolis, Indiana, 46202
Kosair Pediatric Research Unit
Louisville, Kentucky, 40202
About this study
The purpose of this study is to learn more about the safety and dosing of sildenafil in infants.
Read the 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.
- Being tested
- 1 dose of sildenafil
- Keywords
- sildenafil, preterm infants, persistent pulmonary hypertension of the newborn
- Medical subject headings
- Persistent Fetal Circulation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1 dose of sildenafilDrug
Also called Revatio, Viagra
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.
| Study group | Role | What they receive |
|---|---|---|
| sildenafil, standard of care | No intervention | Infants receiving sildenafil as standard of care |
| sildenafil administered for study | Other | 1 dose of sildenafil administered for study Receives: Drug: 1 dose of sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration versus time curve 0-24 hours for sildenafil
Measured: 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
Measured: 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
Clearance of sildenafil
Measured: 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
Measured: 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
Measured: 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 (3)
Number of subjects with adverse events as a measure of safety and tolerability.
Measured: 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
Correlation between serum and dried blood spot samples
Measured: 1-7 days
Evaluate P450 single nucleotide polymorphisms (SNPs)
Measured: 2-7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2012 (estimated)
- Study startFeb 2013
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Persistent Pulmonary Hypertension of the NewbornStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
- Responsible party
- Sponsor
- Investigators
- Matthew M Laughon, MD, MPH, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01670136
- Sponsor's protocol ID
- 11-1646
- Other IDs
- HHSN27500014
- Status last verified
- Nov 2016
- First submitted
- 17 Aug 2012
- Last updated
- 2 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 34741102
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Sildenafil in Premature Infants
- ClinicalTrials.gov ID
- NCT01670136
- Acronym / sponsor ID
- 11-1646
- Keywords
- sildenafil, preterm infants, persistent pulmonary hypertension of the newborn
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
- Study start
- Feb 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 21 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sildenafil, standard of care | No intervention | –Infants receiving sildenafil as standard of care |
| sildenafil administered for study | Other | Drug: 1 dose of sildenafil1 dose of sildenafil administered for study |
Who may qualify
- Ages
- Up to 364 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Gestational age 28 weeks or less receiving sildenafil as standard of care < 365 postnatal days
- 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
Key exclusion criteria (9 listed)
- Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1 dose of sildenafilAlso: Revatio, ViagraA 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. | Drug | sildenafil administered for study |
Primary outcome
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
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
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
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
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
3 secondary outcomes
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
Correlation between serum and dried blood spot samples
Time frame: 1-7 days
Evaluate P450 single nucleotide polymorphisms (SNPs)
Time frame: 2-7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2016.
- Derived from this study: PubMed 34741102Jackson 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew M Laughon, MD, MPH principal investigator
University of North Carolina
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 1 dose of sildenafil in people with Persistent Pulmonary Hypertension of the Newborn, run by University of North Carolina, Chapel Hill at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01670136, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2016.