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

Patent Ductus Arteriosus After Premature Birth Clinical Trial

— SMART-PDA  

Official title:

Selective Early Medical Treatment of the Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05011149
• Other study ID #: 459750
• Status: Recruiting
• Phase: Phase 3
• Start date: January 10, 2022
• Est. completion date: September 30, 2024

Study information

• Verified date: June 2024
• Source: IWK Health Centre
• Contact: Souvik Mitra, MD, MSc
• Phone: +1-902-470-6490
• Email: souvik.mitra[@]iwk.nshealth.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 72 Hours

Eligibility

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

Related Conditions & MeSH terms

• Ductus Arteriosus, Patent
• Patent Ductus Arteriosus After Premature Birth
• Premature Birth

Intervention

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.

Locations

Country	Name	City	State
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	IWK Health Center	Halifax	Nova Scotia
Canada	Centre Hospitalier Universitaire de Quebec	Québec City	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	British Columbia Women's Hospital	Vancouver	British Columbia
United States	OU College of Medicine, University of Oklahoma	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Sharp Mary Birch Hospital for Women & Newborns	San Diego	California

Sponsors (11)

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

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

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

External Links

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