Selective Early Medical Treatment of the Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 9
- 主要终点
- Proportion of eligible infants recruited during the study period
研究概览
简要总结
Background: Among preterm infants, those born at a gestational age less than 26 weeks are considered the most vulnerable with a high risk of short- and long-term health problems that include chronic lung disease, brain bleeds, gut injury, kidney failure and death. Patent ductus arteriosus (PDA) is the most common heart condition with almost 70% preterm infants in this gestational age group being diagnosed with a PDA. Though many PDAs spontaneously resolve on their own, research suggests that if the PDA persists, it may contribute to a number of these short- and long-term health problems. Non-steroidal anti-inflammatory medications such as ibuprofen are commonly used to treat a PDA. Such drugs can also have harmful effects on the gut and kidneys of extremely preterm infants. Therefore, we are unsure if early treatment of a symptomatic PDA in this age group is at all beneficial. Given the wide variation in PDA treatment approaches in this age group, a randomized trial design, where extremely preterm infants with a symptomatic PDA are randomly assigned to early treatment or no early treatment, is essential to address this question.
Purpose of the study: The overall purpose of this pilot study is to assess the feasibility of conducting a large study to explore the following research question: In preterm infants born <26 weeks' gestation, is a strategy of selective early medical treatment of a symptomatic PDA better than no treatment at all in the first week of life?
The main feasibility objectives of this study are:
- To assess how many eligible infants can be enrolled in the study
- To assess how many enrolled infants properly complete the study protocol
Importance: To our knowledge this will be the first study on PDA management in preterm infants that specifically aims to enroll preterm infants born at <26 weeks of gestational age who are at the highest risk for PDA-related problems but have been mostly under-represented in previous PDA studies.
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
- None
入排标准
- 年龄范围
- — 至 72 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Preterm infants less than 26 completed weeks (i.e., up to and including 25 weeks and 6 days) of gestation
排除标准
- •no PDA on initial screening echocardiography
- •congenital heart disease (excluding patent foramen ovale, atrial septal defect or ventricular septal defect with a defect size less than 2mm)
- •other major congenital anomaly
- •decision to withhold/withdraw care
研究组 & 干预措施
Selective early medical treatment (SMART) strategy
Infants who are randomized to experimental group will follow the SMART treatment protocol, which includes echocardiographic screening every 72 hours to categorize PDA disease severity by combining clinical and echocardiographic features. At any evaluation if patients are found to have a "severe PDA" on echocardiography, irrespective of clinical symptoms, or a "moderate PDA" on echocardiography with at least moderate clinical illness, they will receive pharmacotherapy aimed at PDA closure (The PDA severity has been divided into mild, moderate or severe based on pre-defined clinical and echocardiographic criteria).
干预措施: Ibuprofen (Drug)
结局指标
主要结局
Proportion of eligible infants recruited during the study period
时间窗: 7 days postnatal age
Proportion of randomized infants with no reported protocol deviations
时间窗: 7 days postnatal age
次要结局
- Receipt of any PDA pharmacotherapy(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Surgical/interventional PDA closure(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Reasons for non-recruitment(7 days postnatal age)
- All-cause mortality during hospital stay(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Proportion of infants in control group meeting pre-defined safety criteria(7 days postnatal age)
- Reasons for non-adherence to protocol(7 days postnatal age)
- Completeness of data collection for clinical outcomes(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Chronic lung disease(birth through 36 weeks post menstrual age)
- Postnatal corticosteroid use(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Necrotizing enterocolitis(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Definite sepsis(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Oliguria(7 days postnatal age)
- Duration of hospitalization (days)(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Receipt of open-label rescue medical treatment in the control group(7 days postnatal age)
- Pulmonary hemorrhage(7 days postnatal age)
- Duration of invasive mechanical ventilation(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Intraventricular hemorrhage(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Severe intraventricular hemorrhage(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Periventricular leukomalacia(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Gastrointestinal bleeding(within seven days of the first dose of pharmacotherapy)
- Gastrointestinal perforation(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
- Severe retinopathy of prematurity(through hospital discharge (approximately 20 weeks postnatal age unless death occurs first))
研究者
Dr. Souvik Mitra, MD MSc FRCPC
Associate Professor & Neonatologist
IWK Health Centre