Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 109
- 试验地点
- 15
- 主要终点
- Safety as Determined by Adverse Event Experienced by Participants
研究概览
简要总结
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 Office of Orphan Products Development (OOPD).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 7 Days 至 28 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Aspartate Aminotransferase (AST) > 225 U/L < 72 hours prior to randomization
- •Alanine Aminotransferase (ALT) > 150 U/L < 72 hours prior to randomization
研究组 & 干预措施
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.
干预措施: Sildenafil (Drug)
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.
干预措施: Placebo (Other)
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.
干预措施: Sildenafil (Drug)
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.
干预措施: Placebo (Other)
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.
干预措施: Sildenafil (Drug)
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.
干预措施: Placebo (Other)
结局指标
主要结局
Safety as Determined by Adverse Event Experienced by Participants
时间窗: Nonserious adverse events were collected through Day 14 following last study intervention. Serious adverse events were collected through Day 28 following last study intervention. Retinopathy of prematurity was assessed through hospital discharge/transfer.
Description of safety of sildenafil in premature infants and assessed by frequency and incidence of adverse events (AEs) and serious adverse events. Both non-serious and serious adverse events were collected from the time of informed consent through Day 14 after the last study intervention. Serious adverse events were additionally collected through 28 days after the last study intervention. Retinopathy of prematurity (ROP), whether serious or non-serious, was collected through hospital discharge or transfer; hospitalization duration varied based on clinical course, the longest duration was up to 575 days.
次要结局
- Volume of Distribution(Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.)
- Clearance(Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.)
- Half-Life(Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.)
- Area Under the Curve (AUC)(Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.)
- Peak Plasma Concentration(Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.)
- Change in Moderate-severe BPD or Death(From the first day of study drug administration to the end of study drug administration, up to 28 days)