search
Back to results

Selective Early Medical Treatment of Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot RCT (SMART-PDA)

Primary Purpose

Patent Ductus Arteriosus After Premature Birth

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ibuprofen
Sponsored by
IWK Health Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Patent Ductus Arteriosus After Premature Birth focused on measuring extremely preterm infant, early medical treatment, randomized controlled trial

Eligibility Criteria

undefined - 72 Hours (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital of Orange County
  • Sharp Mary Birch Hospital for Women & Newborns
  • Stollery Children's Hospital
  • British Columbia Women's Hospital
  • IWK Health CenterRecruiting
  • Mount Sinai Hospital
  • Sunnybrook Health Sciences Centre
  • Centre Hospitalier Universitaire de Quebec

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Selective early medical treatment (SMART) strategy

Early conservative management strategy

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

Proportion of eligible infants recruited during the study period
Proportion of randomized infants with no reported protocol deviations

Secondary Outcome Measures

Proportion of infants in control group meeting pre-defined safety criteria
Reasons for non-recruitment
qualitative description of reasons for non-recruitment of eligible infants
Reasons for non-adherence to protocol
qualitative description of reasons for non-adherence to protocol in randomized infants
Completeness of data collection for clinical outcomes
Proportion of recruited infants with complete clinical outcome data
All-cause mortality during hospital stay
Surgical/interventional PDA closure
Receipt of any PDA pharmacotherapy
Receipt of open-label rescue medical treatment in the control group
Chronic lung disease
Oxygen or respiratory support requirement at 36 weeks' postmenstrual age or at discharge
Postnatal corticosteroid use
Pulmonary hemorrhage
blood-stained respiratory secretions with a significant increase in respiratory requirements (MAP>12 and/or FiO2>60%)
Duration of invasive mechanical ventilation
Number of days on mechanical ventilation with an endotracheal tube
Intraventricular hemorrhage
Grade I-IV according to Papile Criteria
Severe intraventricular hemorrhage
Grade III-IV according to Papile Criteria
Periventricular leukomalacia
Necrotizing enterocolitis
Stage 2 or greater as per Bell's criteria
Gastrointestinal bleeding
Gastrointestinal perforation
Severe retinopathy of prematurity
stage 3 or greater
Definite sepsis
Clinical symptoms and signs of sepsis and a positive bacterial culture in a specimen obtained from normally sterile fluids or tissue obtained at postmortem
Oliguria
urine output less than 1 mL/kg/hour
Duration of hospitalization (days)

Full Information

First Posted
August 12, 2021
Last Updated
April 2, 2023
Sponsor
IWK Health Centre
Collaborators
BC Children's Hospital Research Institute, CHU de Quebec-Universite Laval, Sunnybrook Health Sciences Centre, Mount Sinai Hospital, Canada, Sharp Mary Birch Hospital for Women & Newborns, Canadian Institutes of Health Research (CIHR), Dalhousie Medical Research Foundation, Children's Hospital of Orange County, OC, California, United States, University of Alberta
search

1. Study Identification

Unique Protocol Identification Number
NCT05011149
Brief Title
Selective Early Medical Treatment of Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot RCT
Acronym
SMART-PDA
Official Title
Selective Early Medical Treatment of the Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 10, 2022 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IWK Health Centre
Collaborators
BC Children's Hospital Research Institute, CHU de Quebec-Universite Laval, Sunnybrook Health Sciences Centre, Mount Sinai Hospital, Canada, Sharp Mary Birch Hospital for Women & Newborns, Canadian Institutes of Health Research (CIHR), Dalhousie Medical Research Foundation, Children's Hospital of Orange County, OC, California, United States, University of Alberta

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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: To assess how many eligible infants can be enrolled in the study 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patent Ductus Arteriosus After Premature Birth
Keywords
extremely preterm infant, early medical treatment, randomized controlled trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Selective early medical treatment (SMART) strategy
Arm Type
Experimental
Arm Description
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).
Arm Title
Early conservative management strategy
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of eligible infants recruited during the study period
Time Frame
7 days postnatal age
Title
Proportion of randomized infants with no reported protocol deviations
Time Frame
7 days postnatal age
Secondary Outcome Measure Information:
Title
Proportion of infants in control group meeting pre-defined safety criteria
Time Frame
7 days postnatal age
Title
Reasons for non-recruitment
Description
qualitative description of reasons for non-recruitment of eligible infants
Time Frame
7 days postnatal age
Title
Reasons for non-adherence to protocol
Description
qualitative description of reasons for non-adherence to protocol in randomized infants
Time Frame
7 days postnatal age
Title
Completeness of data collection for clinical outcomes
Description
Proportion of recruited infants with complete clinical outcome data
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
All-cause mortality during hospital stay
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Surgical/interventional PDA closure
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Receipt of any PDA pharmacotherapy
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Receipt of open-label rescue medical treatment in the control group
Time Frame
7 days postnatal age
Title
Chronic lung disease
Description
Oxygen or respiratory support requirement at 36 weeks' postmenstrual age or at discharge
Time Frame
birth through 36 weeks post menstrual age
Title
Postnatal corticosteroid use
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Pulmonary hemorrhage
Description
blood-stained respiratory secretions with a significant increase in respiratory requirements (MAP>12 and/or FiO2>60%)
Time Frame
7 days postnatal age
Title
Duration of invasive mechanical ventilation
Description
Number of days on mechanical ventilation with an endotracheal tube
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Intraventricular hemorrhage
Description
Grade I-IV according to Papile Criteria
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Severe intraventricular hemorrhage
Description
Grade III-IV according to Papile Criteria
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Periventricular leukomalacia
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Necrotizing enterocolitis
Description
Stage 2 or greater as per Bell's criteria
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Gastrointestinal bleeding
Time Frame
within seven days of the first dose of pharmacotherapy
Title
Gastrointestinal perforation
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Severe retinopathy of prematurity
Description
stage 3 or greater
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Definite sepsis
Description
Clinical symptoms and signs of sepsis and a positive bacterial culture in a specimen obtained from normally sterile fluids or tissue obtained at postmortem
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Title
Oliguria
Description
urine output less than 1 mL/kg/hour
Time Frame
7 days postnatal age
Title
Duration of hospitalization (days)
Time Frame
through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)

10. Eligibility

Sex
All
Maximum Age & Unit of Time
72 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Souvik Mitra, MD, MSc
Phone
+1-902-470-6490
Email
souvik.mitra@iwk.nshealth.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Amish Jain, MBBS, PhD
Email
amish.jain@sinaihealth.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Souvik Mitra, MD, MSc
Organizational Affiliation
Dalhousie University & IWK Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Cleary
Facility Name
Sharp Mary Birch Hospital for Women & Newborns
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jenny Koo
Facility Name
Stollery Children's Hospital
City
Edmonton
State/Province
Alberta
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abbas Hyderi
First Name & Middle Initial & Last Name & Degree
Joseph Ting
Facility Name
British Columbia Women's Hospital
City
Vancouver
State/Province
British Columbia
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Castaldo
Facility Name
IWK Health Center
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3K 6R8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Souvik Mitra
First Name & Middle Initial & Last Name & Degree
Walid El-Naggar
Facility Name
Mount Sinai Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amish Jain
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dany Weisz
Facility Name
Centre Hospitalier Universitaire de Quebec
City
Québec City
State/Province
Quebec
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Audrey Hébert

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All of the individual participant data on clinical outcomes collected during the trial will be shared after deidentification.
IPD Sharing Time Frame
Beginning 6 months following article publication
Links:
URL
https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=441822&lang=en
Description
Project funding information on the Canadian Institutes of Health Research (CIHR) Funding Decision Database

Learn more about this trial

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

We'll reach out to this number within 24 hrs