Safety of Sildenafil in Premature Infants (SIL02)

University of North Carolina (UNC)

Status and phase: Completed; Phase 2

Conditions: Bronchopulmonary Dysplasia

Treatments: Other: Placebo; Drug: Sildenafil

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT03142568

R01FD006099-01

17-2436

75N94022F00001 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 106 patients

Sex: All

Ages: 7 to 28 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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106 participants in 6 patient groups, including a placebo group

Sildenafil cohort 1

Experimental group

Description:

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.

Treatment:

Drug: Sildenafil

Placebo cohort 1

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo

Sildenafil cohort 2

Experimental group

Description:

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.

Treatment:

Drug: Sildenafil

Placebo cohort 2

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo

Sildenafil cohort 3

Experimental group

Description:

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.

Treatment:

Drug: Sildenafil

Placebo cohort 3

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo