Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 125
- 试验地点
- 25
- 主要终点
- Safety Based Upon Number of Participants With Hypotension
研究概览
简要总结
This is a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study of sildenafil in premature infants (inpatient in Neonatal Intensive Care Units (NICUs)) with severe bronchopulmonary dysplasia (BPD).
详细描述
Screening/Baseline
Research staff will document informed consent from the parent/guardian for all participants who satisfy eligibility criteria. The following information will be recorded in the case report form (eCRF) from the clinical medical record:
- Participant demographics, including birth weight and gestational age at birth
- Maternal race/ethnicity
- Medical history
- Physical examination, including actual weight
- All mean arterial pressure (MAP) obtained in the 24 hours before the first dose
- Concomitant medications (within 24 hours prior to start of study drug)
- Respiratory assessment
- Laboratory evaluations
- Echocardiogram: If performed per local standard of care < 14 days prior to start of study drug, a study-specific echocardiogram need not be repeated. If not performed per local standard of care < 14 days prior to start of study drug, an echocardiogram will be required to confirm eligibility.
- Cardiac catheterization reports, if performed per local standard of care < 14 days prior to start of study drug.
- Adverse events following initial study-specific procedure
Treatment Period
The treatment period will include Days 1-28 or last day of study drug if early withdrawal of study drug. The following information will be collected and recorded while the participant is on study drug:
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)
盲法说明
Study drug (sildenafil or placebo) will be prepared in the pharmacy by the unblinded pharmacist. Treatment cohort will be randomly assigned electronically and communicated to the pharmacist via the study portal. All other study staff and the patients/parents will be blinded to the treatment assignment.
入排标准
- 年龄范围
- — 至 29 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented informed consent from parent or guardian, prior to study procedures
- •< 29 weeks gestational age at birth
- •32-44 weeks postmenstrual age
- •Receiving respiratory support at enrollment:
- •If 32 0/7-35 6/7 weeks postmenstrual age: mechanical ventilation (high frequency or conventional)
- •If 36 0/7-44 6/7 weeks postmenstrual age: mechanical ventilation (high frequency or conventional) OR continuous positive airway pressure (CPAP)
- •Criteria 3 and 4 define severe BPD for the purposes of this study
- •CPAP is defined as any of the following:
- •Nasal cannula > 2 liters per minute (LPM)
- •Nasal continuous positive airway pressure (NCPAP)
- •Nasal intermittent positive pressure ventilation (NIPPV)
- •Noninvasive neurally adjusted ventilatory assist (NAVA)
- •Any other device designed to provide positive pressure through a nasal device (e.g., RAM cannula, etc.)
排除标准
- •Previous enrollment and dosing in this study, protocol number (NHLBI-2019-SIL), "Safety of Sildenafil in Premature Infants with Severe Bronchopulmonary Dysplasia (BPD)"
- •Previous exposure to sildenafil within 7 days prior to randomization*
- •Previous exposure to vasopressors within 24 hours prior to randomization*
- •Previous exposure to inhaled nitric oxide within 24 hours prior to randomization*
- •Previous exposure to milrinone within 24 hours prior to randomization*
- •Evidence of pulmonary hypertension or moderate/large patent ductus arteriosus (PDA) on the most recent echocardiogram performed within 14 days prior to randomization
- •Known major congenital heart defect requiring medical or surgical intervention in the neonatal period
- •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
- •Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study.
- •Participant will be reassessed prior to dosing to reconfirm eligibility criteria.
研究组 & 干预措施
Cohort 2, placebo
Placebo (IV or enteral) every 8 hours for 28 days
干预措施: Placebo (Drug)
Cohort 1, placebo
Placebo (IV or enteral) every 8 hours for 28 days
干预措施: Placebo (Drug)
Cohort 3, placebo
Placebo (IV or enteral) every 8 hours for 28 days
干预措施: Placebo (Drug)
Cohort 1, sildenafil
Sildenafil (0.5 mg/kg IV or 1 mg/kg enteral) every 8 hours for 28 days
干预措施: Sildenafil (Drug)
Cohort 2, sildenafil
Sildenafil (1 mg/kg IV or 2 mg/kg enteral) every 8 hours for 28 days
干预措施: Sildenafil (Drug)
Cohort 3, sildenafil
Sildenafil (2 mg/kg IV or 4 mg/kg enteral) every 8 hours for 28 days
干预措施: Sildenafil (Drug)
结局指标
主要结局
Safety Based Upon Number of Participants With Hypotension
时间窗: 28 days post last dose of study drug, up to 9 weeks
Safety as determined by incidence of hypotension experienced by the participants through 28 days post last dose of study drug. Hypotension will be defined as any clinically significant low blood pressure event deemed by the treating physician to require intervention with a fluid bolus or the initiation or escalation of inotropic, vasopressor, or systemic steroid therapy with the specific intent to raise blood pressure.
次要结局
- Central Volume of Distribution (Vc) Population Pharmacokinetics (popPK)(Following the completion of 7 days (168 hours) of study drug administration)
- Peripheral Volume of Distribution (Vp) Population Pharmacokinetics (popPK)(Following the completion of 7 days (168 hours) of study drug administration)
- Clearance Population Pharmacokinetics (popPK)(Following the completion of 7 days (168 hours) of study drug administration)
- Half-life Population Pharmacokinetics (popPK)(Following the completion of 7 days (168 hours) of study drug administration)
- Peak Plasma Concentration Population Pharmacokinetics (popPK)(Following the completion of 7 days (168 hours) of study drug administration)
研究者
Christoph Hornik
Associate Professor of Pediatrics
Duke University