Selective Early Medical Treatment of Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot RCT
- Conditions
- Patent Ductus Arteriosus After Premature Birth
- Interventions
- Registration Number
- NCT05011149
- Lead Sponsor
- IWK Health Centre
- Brief Summary
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:
1. To assess how many eligible infants can be enrolled in the study
2. 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- Preterm infants less than 26 completed weeks (i.e., up to and including 25 weeks and 6 days) of gestation
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Selective early medical treatment (SMART) strategy Ibuprofen 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).
- Primary Outcome Measures
Name Time Method Proportion of eligible infants recruited during the study period 7 days postnatal age Proportion of randomized infants with no reported protocol deviations 7 days postnatal age
- Secondary Outcome Measures
Name Time Method 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 qualitative description of reasons for non-recruitment of eligible infants
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 qualitative description of reasons for non-adherence to protocol in randomized infants
Completeness of data collection for clinical outcomes through hospital discharge (approximately 20 weeks postnatal age unless death occurs first) Proportion of recruited infants with complete clinical outcome data
Chronic lung disease birth through 36 weeks post menstrual age Oxygen or respiratory support requirement at 36 weeks' postmenstrual age or at discharge
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) Stage 2 or greater as per Bell's criteria
Definite sepsis through hospital discharge (approximately 20 weeks postnatal age unless death occurs first) Clinical symptoms and signs of sepsis and a positive bacterial culture in a specimen obtained from normally sterile fluids or tissue obtained at postmortem
Oliguria 7 days postnatal age urine output less than 1 mL/kg/hour
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 blood-stained respiratory secretions with a significant increase in respiratory requirements (MAP\>12 and/or FiO2\>60%)
Duration of invasive mechanical ventilation through hospital discharge (approximately 20 weeks postnatal age unless death occurs first) Number of days on mechanical ventilation with an endotracheal tube
Intraventricular hemorrhage through hospital discharge (approximately 20 weeks postnatal age unless death occurs first) Grade I-IV according to Papile Criteria
Severe intraventricular hemorrhage through hospital discharge (approximately 20 weeks postnatal age unless death occurs first) Grade III-IV according to Papile Criteria
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) stage 3 or greater
Trial Locations
- Locations (9)
Stollery Children's Hospital
🇨🇦Edmonton, Alberta, Canada
Children's Hospital of Orange County
🇺🇸Orange, California, United States
British Columbia Women's Hospital
🇨🇦Vancouver, British Columbia, Canada
Sharp Mary Birch Hospital for Women & Newborns
🇺🇸San Diego, California, United States
OU College of Medicine, University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
IWK Health Center
🇨🇦Halifax, Nova Scotia, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦Québec City, Quebec, Canada