Selective Early Medical Treatment of Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot RCT

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.

Conditions

• Patent Ductus Arteriosus After Premature Birth

Interventions

DRUG

Ibuprofen

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 & Collaborators

• BC Children's Hospital Research Institute

  collaborator OTHER

• CHU de Quebec-Universite Laval

  collaborator OTHER

• Sunnybrook Health Sciences Centre

  collaborator OTHER

• Mount Sinai Hospital, Canada

  collaborator OTHER

• Sharp Mary Birch Hospital for Women & Newborns

  collaborator OTHER

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Dalhousie Medical Research Foundation

  collaborator UNKNOWN

• Children's Hospital of Orange County, OC, California, United States

  collaborator UNKNOWN

• University of Alberta

  collaborator OTHER

• University of Oklahoma

  collaborator OTHER

• IWK Health Centre

  lead OTHER

Principal Investigators

• Souvik Mitra, MD, MSc · Dalhousie University & IWK Health

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

72 Hours

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-01-10

Primary Completion

2024-09-30

Completion

2024-09-30

FDA Drug

Yes

Countries

• United States
• Canada

Study Locations