Clinical trial NCT05011149: Selective Early Medical Treatment of Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot RCT
Official title: Selective Early Medical Treatment of the Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Patent Ductus Arteriosus After Premature Birth
Keywords: extremely preterm infant
early medical treatment
randomized controlled trial
Lead sponsor: IWK Health Centre
Sponsor class: OTHER
Collaborators: name: BC Children's Hospital Research Institute
name: CHU de Quebec-Universite Laval
name: Sunnybrook Health Sciences Centre
name: Mount Sinai Hospital, Canada
name: Sharp Mary Birch Hospital for Women & Newborns
name: Canadian Institutes of Health Research (CIHR)
name: Dalhousie Medical Research Foundation
name: Children's Hospital of Orange County, OC, California, United States
name: University of Alberta
name: University of Oklahoma
First posted: 2021-08-18
Enrollment: 100
Sex: ALL
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of eligible infants recruited during the study period
timeFrame: 7 days postnatal age
measure: Proportion of randomized infants with no reported protocol deviations
timeFrame: 7 days postnatal age
Secondary outcomes:
measure: Proportion of infants in control group meeting pre-defined safety criteria
timeFrame: 7 days postnatal age
measure: Reasons for non-recruitment
timeFrame: 7 days postnatal age
measure: Reasons for non-adherence to protocol
timeFrame: 7 days postnatal age
measure: Completeness of data collection for clinical outcomes
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: All-cause mortality during hospital stay
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Surgical/interventional PDA closure
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Receipt of any PDA pharmacotherapy
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Receipt of open-label rescue medical treatment in the control group
timeFrame: 7 days postnatal age
measure: Chronic lung disease
timeFrame: birth through 36 weeks post menstrual age
measure: Postnatal corticosteroid use
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Pulmonary hemorrhage
timeFrame: 7 days postnatal age
measure: Duration of invasive mechanical ventilation
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Intraventricular hemorrhage
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Severe intraventricular hemorrhage
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Periventricular leukomalacia
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Necrotizing enterocolitis
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Gastrointestinal bleeding
timeFrame: within seven days of the first dose of pharmacotherapy
measure: Gastrointestinal perforation
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Severe retinopathy of prematurity
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Definite sepsis
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
measure: Oliguria
timeFrame: 7 days postnatal age
measure: Duration of hospitalization (days)
timeFrame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Women & Newborns
state: California
city: Oklahoma City
country: United States
facility: OU College of Medicine, University of Oklahoma
state: Oklahoma
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Women's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: IWK Health Center
state: Nova Scotia
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Québec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
Study officials:
affiliation: Dalhousie University & IWK Health
name: Souvik Mitra, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: