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

NCT ID: NCT05011149

Last Updated: 2024-06-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-10

Study Completion Date

2024-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Patent Ductus Arteriosus After Premature Birth

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Selective early medical treatment (SMART) strategy

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).

Group Type EXPERIMENTAL

Ibuprofen

Intervention Type 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.

Early conservative management strategy

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 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
Maximum Eligible Age

72 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BC Children's Hospital Research Institute

OTHER

Sponsor Role collaborator

CHU de Quebec-Universite Laval

OTHER

Sponsor Role collaborator

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role collaborator

Sharp Mary Birch Hospital for Women & Newborns

OTHER

Sponsor Role collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

Dalhousie Medical Research Foundation

UNKNOWN

Sponsor Role collaborator

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

UNKNOWN

Sponsor Role collaborator

University of Alberta

OTHER

Sponsor Role collaborator

University of Oklahoma

OTHER

Sponsor Role collaborator

IWK Health Centre

OTHER

Sponsor Role lead

Responsible Party

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Dr. Souvik Mitra, MD MSc FRCPC

Associate Professor & Neonatologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Souvik Mitra, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Dalhousie University & IWK Health

Locations

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Children's Hospital of Orange County

Orange, California, United States

Site Status RECRUITING

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, United States

Site Status TERMINATED

OU College of Medicine, University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Stollery Children's Hospital

Edmonton, Alberta, Canada

Site Status RECRUITING

British Columbia Women's Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

IWK Health Center

Halifax, Nova Scotia, Canada

Site Status RECRUITING

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status WITHDRAWN

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status WITHDRAWN

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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Souvik Mitra, MD, MSc

Role: CONTACT

+1-902-470-6490

Amish Jain, MBBS, PhD

Role: CONTACT

Facility Contacts

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John Cleary

Role: primary

Marjorie Makoni, MD

Role: primary

Abbas Hyderi

Role: primary

Michael Castaldo

Role: primary

Souvik Mitra

Role: primary

Audrey Hébert

Role: primary

References

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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.

Reference Type DERIVED
PMID: 39053961 (View on PubMed)

Related Links

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https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=441822&lang=en

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

Other Identifiers

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459750

Identifier Type: -

Identifier Source: org_study_id

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