Patent Ductus Arteriosus After Premature Birth
Conditions
Keywords
extremely preterm infant, early medical treatment, randomized controlled trial
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.
Interventions
DRUGIbuprofen
Pharmacotherapy, when indicated (ie, for severe PDA on echocardiography, irrespective of clinical symptoms, or a moderate PDA on echocardiography with at least moderate clinical illness), will be provided in the form of ibuprofen as first line agent at a standard dosing of 10 mg/kg followed by 2 doses of 5mg/kg every 24 h. The route of administration may be intravenous or enteral, as determined by the treating team. For treated infants, follow-up echocardiography will be conducted at the end of the 3-day course and second course of treatment will be initiated if they still fulfill study treatment criteria as mentioned above. If any treatment-eligible infant has a contraindication to ibuprofen, use of acetaminophen will be permitted as an alternative agent.
Sponsors
BC Children's Hospital Research Institute
CHU de Quebec-Universite Laval
Sunnybrook Health Sciences Centre
Mount Sinai Hospital, Canada
Sharp Mary Birch Hospital for Women & Newborns
Canadian Institutes of Health Research (CIHR)
Dalhousie Medical Research Foundation
Children's Hospital of Orange County, OC, California, United States
University of Alberta
University of Oklahoma
IWK Health Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 72 Hours
Healthy volunteers
No
Inclusion criteria
* Preterm infants less than 26 completed weeks (i.e., up to and including 25 weeks and 6 days) of gestation
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Reasons for non-adherence to protocol | 7 days postnatal age | qualitative description of reasons for non-adherence to protocol in randomized infants |
| Necrotizing enterocolitis | through hospital discharge (approximately 20 weeks postnatal age unless death occurs first) | Stage 2 or greater as per Bell's criteria |
| 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 |
| All-cause mortality during hospital stay | 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) | — |
| Receipt of any PDA pharmacotherapy | 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 | — |
| 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) | — |
| Pulmonary hemorrhage | 7 days postnatal age | blood-stained respiratory secretions with a significant increase in respiratory requirements (MAP\>12 and/or FiO2\>60%) |
| Proportion of infants in control group meeting pre-defined safety criteria | 7 days postnatal age | — |
| 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 |
| 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) | — |
| 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 |
| Reasons for non-recruitment | 7 days postnatal age | qualitative description of reasons for non-recruitment of eligible infants |
Countries
Canada, United States
Contacts
Primary ContactSouvik Mitra, MD, MSc
Backup ContactAmish Jain, MBBS, PhD
Outcome results
None listed