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

NCT05011149 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 459750
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 9

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. 1.To assess how many eligible infants can be enrolled in the study
2. 2.To assess how many enrolled infants properly complete the study protocol

Conditions

Patent Ductus Arteriosus After Premature Birth

Keywords

extremely preterm infant; early medical treatment; randomized controlled trial

Outcome Measures

Primary Outcomes (2)

• Proportion of eligible infants recruited during the study period

  7 days postnatal age

• Proportion of randomized infants with no reported protocol deviations

  7 days postnatal age

Secondary Outcomes (22)

• Proportion of infants in control group meeting pre-defined safety criteria

  7 days postnatal age

• Reasons for non-recruitment

  7 days postnatal age

• Reasons for non-adherence to protocol

  7 days postnatal age

• Completeness of data collection for clinical outcomes

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

• All-cause mortality during hospital stay

  through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

Study Arms (2)

Selective early medical treatment (SMART) strategy

EXPERIMENTAL

Infants who are randomized to experimental group will follow the SMART treatment protocol, which includes echocardiographic screening every 72 hours to categorize PDA disease severity by combining clinical and echocardiographic features. At any evaluation if patients are found to have a "severe PDA" on echocardiography, irrespective of clinical symptoms, or a "moderate PDA" on echocardiography with at least moderate clinical illness, they will receive pharmacotherapy aimed at PDA closure (The PDA severity has been divided into mild, moderate or severe based on pre-defined clinical and echocardiographic criteria).

Drug: Ibuprofen

Early conservative management strategy

NO INTERVENTION

Infants randomized to this arm will not undergo any further echocardiographic assessment or pharmacological treatment of the PDA regardless of the clinical signs. If the infant gets an echocardiographic assessment for a reason different than PDA assessment (such as hypotension or oxygenation failure) and a PDA is incidentally noted that fits the treatment criteria, the infant will not be initiated on pharmacotherapy. After 7 days of age, decision on PDA assessment and treatment will be at the discretion of the treating physician.

Interventions

Ibuprofen DRUG

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.

Selective early medical treatment (SMART) strategy

Eligibility Criteria

• Age: Up to 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm infants less than 26 completed weeks (i.e., up to and including 25 weeks and 6 days) of gestation

You may not qualify if:

• 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

Sponsors & Collaborators

• IWK Health Centre: lead
• BC Children's Hospital Research Institute: collaborator
• CHU de Quebec-Universite Laval: collaborator
• Sunnybrook Health Sciences Centre: collaborator
• Mount Sinai Hospital, Canada: collaborator
• Sharp Mary Birch Hospital for Women & Newborns: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Dalhousie Medical Research Foundation: collaborator
• Children's Hospital of Orange County, OC, California, United States: collaborator
• University of Alberta: collaborator
• University of Oklahoma: collaborator

Study Sites (9)

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, 92123, United States

TERMINATED

OU College of Medicine, University of Oklahoma

Oklahoma City, Oklahoma, 73117, United States

RECRUITING

Stollery Children's Hospital

Edmonton, Alberta, Canada

RECRUITING

British Columbia Women's Hospital

Vancouver, British Columbia, Canada

RECRUITING

IWK Health Center

Halifax, Nova Scotia, B3K 6R8, Canada

RECRUITING

Mount Sinai Hospital

Toronto, Ontario, Canada

WITHDRAWN

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

WITHDRAWN

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, Canada

RECRUITING

Related Publications (1)

• Mitra S, Hebert A, Castaldo M, Disher T, El-Naggar W, Dhillon S, Alhassen Z, Koo J, Katheria AC, Hyderi A, Kumaran K, Makoni M, Weisz DE, Jain A, Bacchini F, Cameron A, Hatfield T, Dorling J, McNamara PJ, Thabane L. Selective early medical treatment of the patent ductus arteriosus in extremely low gestational age infants: a pilot randomised controlled trial protocol (SMART-PDA). BMJ Open. 2024 Jul 24;14(7):e087998. doi: 10.1136/bmjopen-2024-087998.

  PMID: 39053961 DERIVED

Related Links

• Project funding information on the Canadian Institutes of Health Research (CIHR) Funding Decision Database

MeSH Terms

Interventions

Ibuprofen

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Souvik Mitra, MD, MSc

  Dalhousie University & IWK Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Souvik Mitra, MD, MSc

CONTACT

+1-902-470-6490; souvik.mitra@iwk.nshealth.ca

Amish Jain, MBBS, PhD

CONTACT

amish.jain@sinaihealth.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor & Neonatologist

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: August 18, 2021
• Study Start: January 10, 2022
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: As soon as possible, wherever legally and ethically possible. In addition, data from the trial will be made available upon reasonable request.

Locations

CA (6); US (3)