Randomized Controlled Trials
SPIN Pilot RCT – Lead Site
Single-dose Prophylactic Indomethacin in Extremely Preterm Infants – A Multicenter Pilot Randomized Blinded Placebo-Controlled Trial
Each year in Canada, approximately 900 infants are born extremely preterm at less than 26 weeks gestation (GA. Nearly four out of 10 of these infants will not survive or develop a devastating neurological complication called severe intraventricular hemorrhage (sIVH). Existing evidence shows that a 3-dose regimen of intravenous indomethacin (0.1mg/kg/dose every 24h for 3 doses), given shortly after birth, significantly reduces the incidence of death and severe brain injury. However, use of this conventional regimen has declined due to concerns about potential gastrointestinal side effects.
Recent pharmacokinetic studies show that indomethacin clearance is significantly reduced in the first week of life of infants born ≤26 weeks GA due to their developmental immaturity. As a result, a single 0.1 mg/kg dose maintains therapeutic levels for at least 72h – the most critical period for sIVH onset in these smallest infants.
This pilot trial will assess the feasibility of conducting a definitive trial to explore the following research question: In extremely preterm infants born <26 weeks GA, does a single prophylactic dose of intravenous indomethacin (0.1 mg/kg)), given within 12 hours of birth, reduce morbidity and mortality compared to a saline placebo?
ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT06572917
CIHR Funding: https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=523450&lang=en
For more information about the study, contact the study coordinator at michelle.avina@cw.bc.ca.
Prospective Clinical Studies
The impact of low dose dexamethasone (DART) treatment in neonates on echocardiographic markers of cardiac function and pulmonary hypertension (Dr. Judith Leyens)
Approximately 10% of all babies are born prematurely and one of the most common complications associated with prematurity is chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD). Complex cardiovascular interplay can further predispose these vulnerable infants to develop pulmonary hypertension (PH), a serious and potentially life-threatening condition. While many different approaches exist to prevent and treat evolving or established BPD, postnatal corticosteroids are one of the most commonly used. However, previous studies have been limited by small sample sizes and short-term follow-up periods, typically 7-14 days post-treatment. Our study aims to address these gaps by prospectively evaluating the echocardiographic and clinical impact of low-dose dexamethasone treatment (DART) in a larger cohort of extremely preterm infants (<28 weeks gestational age), with assessments conducted up to 72 hours before and after DART, as well as at 32 weeks gestational age, to capture both immediate and longer-term outcomes.
For more information about the study, contact the research coordinator at michelle.avina@cw.bc.ca.
Retrospective Studies
Prophylactic Indomethacin in MicropreemiEs: A Retrospective Cohort Study (PRIME) – Una Spasovski
Severe intraventricular hemorrhage (sIVH) remains a major contributor to morbidity and mortality among micropreemies. Clinical trials have shown that prophylactic indomethacin reduces the incidence of sIVH, an outcome deemed critical by families. However, its use remains inconsistent due to concerns about potential adverse effects. To address this gap, Una led a retrospective cohort study linking data from the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN). The study will evaluate whether prophylactic indomethacin improves survival at NICU discharge and reduces significant neurodevelopmental impairment at 18–24 months in infants born at less than 26 weeks’ gestation.
This project, Prophylactic Indomethacin in Micropreemies (PRIME), has been presented at several national and international conferences, including the CNN Annual Meeting (Feb 11, 2025), CANTRAIN's 2nd National Conference (Feb 25, 2025), Neonatal Follow-Up Program Research Day (April 4, 2025), UBC Department of Pediatrics Celebrate Research Day (April 11, 2025), Pediatric Academic Societies Meeting (April 28, 2025) and the Canadian National Perinatal Research Meeting (May 13, 2025).
Impact of Patent Ductus Arteriosus (PDA) on Echocardiographic Markers of Chronic Pulmonary Hypertension: A SMART-PDA Sub Study – Caia Fisher-Hulse
The ductus arteriosus is a developmental shunt that allows oxygenated blood to by-pass the fluid filled lungs during fetal life. In preterm infants, whose cardiopulmonary systems are underdeveloped at birth, this duct can remain open leading to a congenital heart defect called patent ductus arteriosus (PDA). PDA affects approximately 60% of infants born before 29 weeks of gestation and prolonged exposure can lead to severe adverse outcomes, including chronic pulmonary hypertension (cPH), increased morbidity, and mortality. This project will use targeted neonatal echocardiography (TNE) to explore the complex hemodynamic relationship between PDA and chronic pulmonary hypertension (cPH) in extremely preterm infants born before 26 weeks gestation.
This project was presented at the UBC Women+ and Children’s Health Sciences (WACH) Research Day (March 2025).
SMART-PDA Lite: Examining the validity of a simplified SMART-PDA treatment algorithm - Caia Fisher-Hulse
The decision to treat versus not treat patent ductus arteriosus (PDA) in micropreemies may be reached with reduced clinical and echocardiographic criteria. This study explores whether a simplified selective early medical treatment criteria (SMART-PDA lite) can lead to the same treatment decisions as the original SMART criteria. Simplified echocardiographic and clinical treatment criteria may lead to determining who to treat with greater ease, and increased implementation of the SMART strategy.
This project was presented at the 2025 NeoHeart Conference in San Diego (July 29-August 1, 2025).
Reliability of two-dimensional mode versus M-mode echocardiography for measurement of left atrium/aortic diameter ratio and fractional shortening in extreme preterm infants – Dr. Uthaya K. Kanagaraj
In extremely preterm infants, targeted neonatal echocardiography (TNE) is increasingly used to assess the hemodynamic status of newborns with patent ductus arteriosus (PDA). Two TNE measurements used to evaluate hemodynamically significant PDA are the left atrium to aortic root ratio (LA:Ao), which reflects left heart volume overload, and fractional shortening (FS), which assesses left ventricular function. These parameters are most commonly measured using M-mode imaging in current TNE protocols. However, this practice differs from the American Society of Echocardiography pediatric guidelines, which recommend using 2D-imaging for FS and offer no specific guidance for LA:AO measurement. This study aims to evaluate the interrater reliability of M-mode versus 2D-mode measurements of LA:Ao and FS in infants born before 29 weeks gestation.
This study was presented as an oral presentation at the E2i Research Day (Feb 25, 2025), NICU Research and Quality Improvement Rounds (March 14, 2025) and in the recently concluded Pediatric Academic Societies Meeting in Hawaii as a poster presentation.
Evidence Synthesis
Early erythropoiesis-simulating agents in preterm or low birth weight infants: update of a Cochrane Systematic Review – Dr. Kia Anarna
We have updated the evidence through a systematic review of randomized controlled trials on the efficacy of early erythropoiesis-stimulating agents such as erythropoietin and darbepoetin among preterm and low birth weight infants on outcomes such as mortality, neurodevelopmental impairment, retinopathy of prematurity, necrotizing enterocolitis, severe intraventricular hemorrhage, and number of transfusions among others. Certainty of evidence was assessed using GRADE and subgroup analysis of high-quality trials was done. Erythropoietin was found to have consistent hematopoietic benefits among preterm and low birth weight infants with a relatively good safety profile.
This project has been presented as an oral presentation at the Neonatal Follow-up Research Day (April4, 2025), UBC Department of Pediatrics Celebrate Research Day (2nd place best fellow research, April 11, 2025), Pediatric Academic Societies Meeting in Honolulu (April 27, 2025), and the District VIII Conference in Boise Idaho (June 6, 2025).
Recently Completed Projects
SMART-PDA Pilot RCT- awaiting publication
Trial registration: https://clinicaltrials.gov/study/NCT05011149
Protocol: https://bmjopen.bmj.com/content/14/7/e087998
CANRxPDA - awaiting publication
Study registration: https://clinicaltrials.gov/study/NCT04347720
Protocol: https://bmjopen.bmj.com/content/11/5/e050682.long