Patent Ductus Arteriosus After Premature BirthPhase 3SMART-PDANCT05011149
Selective Early Medical Treatment of Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot RCT
A Phase 3 study testing Ibuprofen in people with Patent Ductus Arteriosus After Premature Birth, run by IWK Health Centre at 9 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages Up to 72 hours
- Conditions the study is for
- Patent Ductus Arteriosus After Premature Birth
- What is being tested?
- Ibuprofen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 10 Jan 2022to 30 Sep 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 72 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Preterm infants less than 26 completed weeks (i.e., up to and including 25 weeks and 6 days) of gestation
Who cannot join
- 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
Trial locations and contacts
9 sites in 2 countries.
Amish Jain, MBBS, PhD contact
9 sites in 2 countries
Canada6 sites, 4 recruiting
- Recruiting
Stollery Children's Hospital
Edmonton, Alberta
Abbas Hyderi
Joseph Ting
- Recruiting
IWK Health Center
Halifax, Nova Scotia, B3K 6R8
Souvik Mitra
Walid El-Naggar
- Recruiting
Centre Hospitalier Universitaire de Quebec
Québec, Quebec
Audrey Hébert
- Withdrawn
Mount Sinai Hospital
Toronto, Ontario
- Withdrawn
Sunnybrook Health Sciences Centre
Toronto, Ontario
- Recruiting
British Columbia Women's Hospital
Vancouver, British Columbia
Michael Castaldo
United States3 sites, 2 recruiting
- Recruiting
OU College of Medicine, University of Oklahoma
Oklahoma City, Oklahoma, 73117
Marjorie Makoni, MD
- Recruiting
Children's Hospital of Orange County
Orange, California, 92868
John Cleary
- Terminated
Sharp Mary Birch Hospital for Women & Newborns
San Diego, California, 92123
About this study
Official title: Selective Early Medical Treatment of the Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot Randomized Controlled Trial
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?
Read more
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.
- Being tested
- Ibuprofen
- Keywords
- extremely preterm infant, early medical treatment, randomized controlled trial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbuprofenDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of eligible infants recruited during the study period
Measured: 7 days postnatal age
Proportion of randomized infants with no reported protocol deviations
Measured: 7 days postnatal age
Secondary outcomes (22)
Proportion of infants in control group meeting pre-defined safety criteria
Measured: 7 days postnatal age
Reasons for non-recruitment
qualitative description of reasons for non-recruitment of eligible infants
Measured: 7 days postnatal age
Reasons for non-adherence to protocol
qualitative description of reasons for non-adherence to protocol in randomized infants
Measured: 7 days postnatal age
Completeness of data collection for clinical outcomes
Proportion of recruited infants with complete clinical outcome data
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
All-cause mortality during hospital stay
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Surgical/interventional PDA closure
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Receipt of any PDA pharmacotherapy
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Receipt of open-label rescue medical treatment in the control group
Measured: 7 days postnatal age
Chronic lung disease
Oxygen or respiratory support requirement at 36 weeks' postmenstrual age or at discharge
Measured: birth through 36 weeks post menstrual age
Postnatal corticosteroid use
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Pulmonary hemorrhage
blood-stained respiratory secretions with a significant increase in respiratory requirements (MAP>12 and/or FiO2>60%)
Measured: 7 days postnatal age
Duration of invasive mechanical ventilation
Number of days on mechanical ventilation with an endotracheal tube
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Intraventricular hemorrhage
Grade I-IV according to Papile Criteria
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Severe intraventricular hemorrhage
Grade III-IV according to Papile Criteria
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Periventricular leukomalacia
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Necrotizing enterocolitis
Stage 2 or greater as per Bell's criteria
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Gastrointestinal bleeding
Measured: within seven days of the first dose of pharmacotherapy
Gastrointestinal perforation
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Severe retinopathy of prematurity
stage 3 or greater
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
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
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Oliguria
urine output less than 1 mL/kg/hour
Measured: 7 days postnatal age
Duration of hospitalization (days)
Measured: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2021
- Study start10 Jan 2022
- Primary completion30 Sep 2024 (estimated)
- Study completion30 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Patent Ductus Arteriosus After Premature BirthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IWK Health Centre
- Sponsor type
- University, hospital or other
- 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, University of Alberta, University of Oklahoma
- Responsible party
- Principal investigator, Dr. Souvik Mitra, MD MSc FRCPC, IWK Health Centre
- Investigators
- Souvik Mitra, MD, MSc, Principal investigator, Dalhousie University & IWK Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05011149
- Sponsor's protocol ID
- 459750
- Acronym
- SMART-PDA
- Status last verified
- Jun 2024
- First submitted
- 12 Aug 2021
- Last updated
- 21 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data on clinical outcomes collected during the trial will be shared after deidentification.
Publications
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.
PubMed 39053961
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selective Early Medical Treatment of the Patent Ductus Arteriosus in Extremely Low Gestational Age Infants: A Pilot Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05011149
- Acronym / sponsor ID
- SMART-PDA / 459750
- Keywords
- extremely preterm infant, early medical treatment, randomized controlled trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- IWK Health CentreUniversity, hospital or other
- 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, University of Alberta, University of Oklahoma
- Study start
- 10 Jan 2022 (actual)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 30 Sep 2024 (estimated)
- First posted
- 18 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Selective early medical treatment (SMART) strategy | Experimental | Drug: IbuprofenInfants 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). |
| 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. |
Who may qualify
- Ages
- Up to 72 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Preterm infants less than 26 completed weeks (i.e., up to and including 25 weeks and 6 days) of gestation
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbuprofenPharmacotherapy, 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. | Drug | Selective early medical treatment (SMART) strategy |
Primary outcome
Proportion of eligible infants recruited during the study period
Time frame: 7 days postnatal age
Proportion of randomized infants with no reported protocol deviations
Time frame: 7 days postnatal age
22 secondary outcomes
Proportion of infants in control group meeting pre-defined safety criteria
Time frame: 7 days postnatal age
Reasons for non-recruitment
Time frame: 7 days postnatal age
Reasons for non-adherence to protocol
Time frame: 7 days postnatal age
Completeness of data collection for clinical outcomes
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
All-cause mortality during hospital stay
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Surgical/interventional PDA closure
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Receipt of any PDA pharmacotherapy
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Receipt of open-label rescue medical treatment in the control group
Time frame: 7 days postnatal age
Chronic lung disease
Time frame: birth through 36 weeks post menstrual age
Postnatal corticosteroid use
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Pulmonary hemorrhage
Time frame: 7 days postnatal age
Duration of invasive mechanical ventilation
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Intraventricular hemorrhage
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Severe intraventricular hemorrhage
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Periventricular leukomalacia
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Necrotizing enterocolitis
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Gastrointestinal bleeding
Time frame: within seven days of the first dose of pharmacotherapy
Gastrointestinal perforation
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Severe retinopathy of prematurity
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Definite sepsis
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Oliguria
Time frame: 7 days postnatal age
Duration of hospitalization (days)
Time frame: through hospital discharge (approximately 20 weeks postnatal age unless death occurs first)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2024.
- Derived from this study: PubMed 39053961Mitra 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.
- Project funding information on the Canadian Institutes of Health Research (CIHR) Funding Decision DatabaseLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All of the individual participant data on clinical outcomes collected during the trial will be shared after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amish Jain, MBBS, PhD contact
Souvik Mitra, MD, MSc principal investigator
Dalhousie University & IWK Health
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ibuprofen in people with Patent Ductus Arteriosus After Premature Birth, run by IWK Health Centre at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Souvik Mitra, MD, MSc (+1-902-470-6490, souvik.mitra@iwk.nshealth.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of eligible infants recruited during the study period (time frame: 7 days postnatal age). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05011149, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2024.