Paracetamol Versus Ibuprofen in Premature Infants With Hemodynamically Significant Patent Ductus Arteriosus: a Randomized Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 133
- 试验地点
- 4
- 主要终点
- Rate of closure of the hsPDA after treatment with paracetamol (experimental drug) versus ibuprofen (control drug).
研究概览
简要总结
Multicentric, double-blind clinical trial, which will evaluate the efficacy of iv paracetamol versus standard treatment with ibuprofen in the closure of patent ductus arteriosus in the preterm newborn. Secondarily, we intend to compare the safety of both treatments, increase our knowledge about the pharmacokinetics, pharmacodynamics and pharmacogenetics of paracetamol and ibuprofen in the neonatal period and make a pharmacoeconomic assessment of the use of both drugs.
详细描述
Those newborns ≤ 30 weeks of gestational age who are diagnosed in the first 2 weeks of hemodynamically significant ductus arteriosus and who do not meet any exclusion criteria will be eligible to participate in the study.
The PARACETAMOL group will receive intravenous doses of 15 mg/kg administered every 6h for 3 days (up to a maximum of 2 courses, i.e. 6 days). The IBUPROFEN group (control group) will receive the usual treatment, this is an initial dose of 10 mg/kg followed by 5 mg/kg intravenously at 24 and 48 hours after the first (all three doses are considered a treatment course), up a maximum of 2 courses).
A daily echocardiographic control will be performed to evaluate the closure of the ductus. If the ductus remains open and with significant clinical repercussion after completing a 3-day course of treatment, another batch of 3 doses of the same treatment will be administered. If medical treatment fails after two courses (6 days), the possibility of administering a batch of Ibuprofen at usual doses in both groups with the intention of offering standard treatment to all patients will be considered. Once the medical treatment with both drugs is completed if the ductus remains significant, the surgical closure will be carried out.
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
- — 至 14 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written Informed consent of parents/guardians
- •Gestacional Age ≤30 weeks
- •Postnatal age ≤ 2 weeks
- •Need for ventilatory support
- •Born in participating hospital/arrival to them within the period of application of the treatment
- •1 st episode of hemodynamically significant Patent Ductus Arteriosus
排除标准
- •Major congenital malformations or chromosomopathies
- •Refusal to participate and / or sign the informed consent.
- •Impossibility or erroneous randomization
- •Participation in another clinical trial with drugs
- •Diuresis less than 1 ml / kg / h for 8 h prior to treatment
- •Greater than 1.8 mg / dl Creatinine
- •Platelets below 50,000 / uL
- •Active bleeding (tracheal, gastrointestinal and renal)
- •Intraventricular hemorrhage recently (48h) (grades 3-4)
- •Severe hyperbilirubinemia
- •Liver failure or severe coagulopathy
- •Active necrotizing enterocolitis or intestinal perforation
- •Septic shock
- •Imminent death
研究组 & 干预措施
Ibuprofen
Intravenous ibuprofen 10 mg/kg/24 h (day 1) and 5 mg/kg/24h (day 2 and 3) for 3 or 6 days
干预措施: Ibuprofen (Drug)
Paracetamol
Intravenous paracetamol 15 mg/kg/6h for 3 or 6 days
干预措施: Paracetamol (Drug)
结局指标
主要结局
Rate of closure of the hsPDA after treatment with paracetamol (experimental drug) versus ibuprofen (control drug).
时间窗: 24-48 hours after the completion of study intervention
It will include the closure rate after the first course of treatment, considered as ductus diameter \< 1 mm monitored by echocardiography performed by a pediatric cardiology specialist.
次要结局
- Need for surgical ligation(from randomization until discharge, an average of 2 months)
- Need for rescue treatment after two courses of treatment(from randomization until discharge, an average of 2 months)
- Need for a second course of treatment(from randomization until discharge, an average of 2 months)
- Closure rate after two treatment courses(from randomization until discharge, an average of 2 months)
- Reopening rate after closure(from randomization until discharge, an average of 2 months)
- Closing rate after reopening(from randomization until discharge, an average of 2 months)
- Incidence of early complications(from randomization until discharge, an average of 2 months)
- Incidence of late complications(from randomization until 2 years)
- Pharmacodynamics model of paracetamol in the context of hsPDA: Maximum Plasma Concentration [Cmax](24-48 hours after the completion of study intervention)
- Pharmacodynamics model of paracetamol in the context of hsPDA: Minimum Plasma Concentration [Cmin](24-48 hours after the completion of study intervention)
- Pharmacodynamics model of paracetamol in the context of hsPDA: Area Under the Curve [AUC])(24-48 hours after the completion of study intervention)
- Time required until closing(from randomization until discharge, an average of 2 months)
- Pharmacodynamics model of paracetamol in the context of hsPDA: urine metabolites(24-48 hours after the completion of study intervention)
- Pharmacogenetics of paracetamol(24-48 hours after the completion of study intervention)
- Genotoxicity mesured by %DNA damage(from randomization until discharge, an average of 2 months)
- Price-effectiveness ratio. Cost-effectiveness analysis depending on the efficiency obtained in the treatment.(from randomization until discharge, an average of 2 months)
研究者
Máximo Vento Torres
Scientific Director Health Research Institute La Fe
Instituto de Investigacion Sanitaria La Fe