Safety of Sildenafil in Premature Infants

NCT ID: NCT03142568

Last Updated: 2025-03-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

106 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-02

Study Completion Date

2025-01-03

Brief Summary

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Describe the safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia and determine preliminary effectiveness and pharmacokinetics (PK) of sildenafil. Funding Source - FDA OOPD.

Detailed Description

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This will be a multi-center, randomized, placebo-controlled, sequential dose escalating, double masked, safety data study of sildenafil in premature infants.

This is a Phase II study design, premature infants (inpatient in neonatal intensive care units) will be randomized in a dose escalating approach 3:1 (sildenafil: placebo) into 3 cohorts with escalating doses of sildenafil. There will be 40 randomized and dosed participants in each cohort for a total of up to 120 participants. Cohort 1 sildenafil dose will be 0.125 mg/kg q 8 hours IV or 0.25 mg/kg q 8 hours enteral. Cohort 2 sildenafil dose will be 0.5 mg/kg q 8 hours IV or 1.0 mg/kg q 8 hours enteral. Cohort 3 sildenafil dose will be 1 mg/kg q 8 hours IV or 2 mg/kg q 8 hours enteral.

Conditions

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Bronchopulmonary Dysplasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Sildenafil cohort 1

Within cohort 1 infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. Infants randomized to sildenafil will receive 0.125 mg/kg daily every 8 hours intravenously (IV), or 0.25 mg/kg daily every 8 hours enterally for 28 days.

Group Type EXPERIMENTAL

Sildenafil

Intervention Type DRUG

Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.

Placebo cohort 1

Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Infants randomized to the placebo group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).

Sildenafil cohort 2

Cohort 2 infants will receive sildenafil 0.5 mg/kg daily every 8 hours intravenously (IV) or 1 mg/kg daily every 8 hours enterally for 28 days.

Group Type EXPERIMENTAL

Sildenafil

Intervention Type DRUG

Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.

Placebo cohort 2

Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Infants randomized to the placebo group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).

Sildenafil cohort 3

Cohort 3 infants will receive sildenafil 1 mg/kg daily every 8 hours intravenously (IV) or 2 mg/kg daily every 8 hours enterally for 28 days.

Group Type EXPERIMENTAL

Sildenafil

Intervention Type DRUG

Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.

Placebo cohort 3

Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Infants randomized to the placebo group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).

Interventions

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Sildenafil

Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.

Intervention Type DRUG

Placebo

Infants randomized to the placebo group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).

Intervention Type OTHER

Other Intervention Names

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Revatio sugar water

Eligibility Criteria

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Inclusion Criteria

* Receiving positive airway pressure (nasal continuous airway pressure, nasal intermittent positive pressure ventilation, or nasal cannula flow \> 1LPM) or mechanical ventilation (high frequency or conventional)
* \<29 weeks gestational age at birth
* 7-28 (inclusive) days postnatal age at time of randomization

Exclusion Criteria

* Currently receiving vasopressors
* Currently receiving inhaled nitric oxide
* Baseline mean arterial pressure \< gestational age (in weeks) plus postnatal age (in weeks) within 2 hours of sildenafil administration
* Known allergy to sildenafil
* Known sickle cell disease
* AST \> 225 U/L \< 72 hours prior to randomization
* ALT \> 150 U/L \< 72 hours prior to randomization
Minimum Eligible Age

7 Days

Maximum Eligible Age

28 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duke University

OTHER

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthew M Laughon, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

University of Florida College of Medicine Jacksonville-Wolfson Children's Hospital

Jacksonville, Florida, United States

Site Status

University of Florida Jacksonville Shands Medical Center

Jacksonville, Florida, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Wesley Medical Center

Wichita, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Ochsner Baptist Medical Center

New Orleans, Louisiana, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Children's Hospital of Nevada at UMC

Las Vegas, Nevada, United States

Site Status

Monmouth Medical Center

Long Branch, New Jersey, United States

Site Status

Cohen Children's Medical Center of NY

New Hyde Park, New York, United States

Site Status

Golisano Children's Hospital - University of Rochester Medical Center

Rochester, New York, United States

Site Status

WakeMed Health and Hospitals

Raleigh, North Carolina, United States

Site Status

University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

Health Sciences Centre Hospital

Winnipeg, Manitoba, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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75N94022F00001

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

R01FD006099-01

Identifier Type: FDA

Identifier Source: secondary_id

View Link

17-2436

Identifier Type: -

Identifier Source: org_study_id

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