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

Souvik Mitra, Amish Jain, Joseph Y. Ting, Nadya Ben Fadel, Christine Drolet, Ayman Abou Mehrem, Amuchou Soraisham, Bonny Jasani, Deepak Louis, Anie Lapointe, Jon Dorling, Faiza Khurshid, Abbas Hyderi, Kumar Kumaran, Jaya Bodani, Dany Weisz, Ruben Alvaro, Mohammed Adie, Miroslav Stavel, Alyssa MorinSoume Bhattacharya, Jaideep Kanungo, Rody Canning, Xiang Y. Ye, Tara Hatfield, Courtney E. Gardner, Prakesh Shah

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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's 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.

Original languageEnglish
Article numbere050682
JournalBMJ Open
Volume11
Issue number5
DOIs
Publication statusPublished - May 5 2021

Bibliographical note

Funding Information:
Funding This work is supported by the Canadian Institutes of Health Research

Funding Information:
(CIHR) Project grant (428014) [https://webapps.cihr-irsc.gc.ca/decisions/p/project_ details.html?applId=410247&lang=en].

Publisher Copyright:
© 2021 BMJ Publishing Group. All rights reserved.

ASJC Scopus Subject Areas

  • General Medicine

PubMed: MeSH publication types

  • Clinical Trial Protocol
  • Journal Article
  • Research Support, Non-U.S. Gov't

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