Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: A protocol for a multicentre comparative effectiveness study (CANRxPDA)

Introduction Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants. Methods and analysis A multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born 29 weeks gestational age with an echocardiography confirmed PDA will be conducted. All participating sites will self-select and adhere to one of the following primary pharmacotherapy protocols for all preterm babies who are deemed to require treatment. Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous). Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy). Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3-7 days. Intravenous indomethacin (0.1-0.3 mg/kg intravenous every 12-24 hours for a total of three doses). Outcomes The primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment. Sites and sample size The study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years. Analysis To examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ 2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ 2 test, Student\u27s t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach. Ethics and dissemination The study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres. © 2021 Author(s). Published by BMJ

Surfactant delivery via thin catheter in preterm infants: A systematic review and meta-analysis

Objective Surfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory distress syndrome (RDS); however, the benefits particularly in infants Methods Medical databases were searched until December 2022 for randomized controlled trials (RCTs) assessing STC compared to controls that included intubation for surfactant or nCPAP in preterm infants with RDS. The primary outcome was bronchopulmonary dysplasia (BPD) at 36 weeks gestation in survivors. Subgroup analysis was conducted comparing STC to controls in infants Results Twenty-six RCTs of 3349 preterm infants, in which half of the studies had low risk of bias, were included. STC decreased the risk of BPD in survivors compared to controls (17 RCTs; N = 2408; relative risk (RR) = 0.66; 95% confidence interval (CI) 0.51 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) = 13; CoE: moderate). In infants Conclusions Compared to controls, STC may be a more efficacious and safe method of surfactant delivery in preterm infants with RDS, including infants < 29 weeks’ gestation

Surfactant delivery via thin catheter in preterm infants: A systematic review and meta-analysis.

ObjectiveSurfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory distress syndrome (RDS); however, the benefits particularly in infants MethodsMedical databases were searched until December 2022 for randomized controlled trials (RCTs) assessing STC compared to controls that included intubation for surfactant or nCPAP in preterm infants with RDS. The primary outcome was bronchopulmonary dysplasia (BPD) at 36 weeks gestation in survivors. Subgroup analysis was conducted comparing STC to controls in infants ResultsTwenty-six RCTs of 3349 preterm infants, in which half of the studies had low risk of bias, were included. STC decreased the risk of BPD in survivors compared to controls (17 RCTs; N = 2408; relative risk (RR) = 0.66; 95% confidence interval (CI) 0.51 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) = 13; CoE: moderate). In infants ConclusionsCompared to controls, STC may be a more efficacious and safe method of surfactant delivery in preterm infants with RDS, including infants < 29 weeks' gestation

Forest plot of STC versus controls for BPD or death.

Forest plot of STC versus controls for BPD or death.</p

Forest plot of STC versus controls for BPD or death in infants < 29 weeks’ with RDS.

Forest plot of STC versus controls for BPD or death in infants < 29 weeks’ with RDS.</p

Forest plots of STC versus controls for need for an additional dose of surfactant in preterm infants with RDS.

Forest plots of STC versus controls for need for an additional dose of surfactant in preterm infants with RDS.</p

Forest plots of STC versus controls for Bayley MDI in preterm infants with RDS.

Forest plots of STC versus controls for Bayley MDI in preterm infants with RDS.</p

Forest plot of STC versus controls for pneumothorax in infants < 29 weeks’ with RDS.

Forest plot of STC versus controls for pneumothorax in infants < 29 weeks’ with RDS.</p

PRISMA 2020 checklist.

ObjectiveSurfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory distress syndrome (RDS); however, the benefits particularly in infants MethodsMedical databases were searched until December 2022 for randomized controlled trials (RCTs) assessing STC compared to controls that included intubation for surfactant or nCPAP in preterm infants with RDS. The primary outcome was bronchopulmonary dysplasia (BPD) at 36 weeks gestation in survivors. Subgroup analysis was conducted comparing STC to controls in infants ResultsTwenty-six RCTs of 3349 preterm infants, in which half of the studies had low risk of bias, were included. STC decreased the risk of BPD in survivors compared to controls (17 RCTs; N = 2408; relative risk (RR) = 0.66; 95% confidence interval (CI) 0.51 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) = 13; CoE: moderate). In infants ConclusionsCompared to controls, STC may be a more efficacious and safe method of surfactant delivery in preterm infants with RDS, including infants </div

Forest plots of STC versus controls for need for intubation at 72 hours of life in preterm infants with RDS.

Forest plots of STC versus controls for need for intubation at 72 hours of life in preterm infants with RDS.</p