Bronchopulmonary DysplasiaNCT05915806
Enteral High-dose DHA Supplementation on Bronchopulmonary Dysplasia in Very Preterm Infants: a Collaborative Study
A study testing High-dose DHA in people with Bronchopulmonary Dysplasia and Child Development, run by CHU de Quebec-Universite Laval at 1 site in Canada.
Trial summary
This one-stage individual participant data (IPD) meta-analysis study will aim to determine whether high-dose docosahexaenoic acid (DHA) enteral supplementation during the neonatal period is associated with the risk for severe bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (PMA) compared to control, in… Read more about this study
- Who is it for?
- Ages Up to 14 weeksHealthy volunteers can take part
- Conditions the study is for
- Bronchopulmonary Dysplasia, Child Development, Neonatal and Perinatal Conditions
- What is being tested?
- High-dose DHA
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,801 participants
- Where
- 1 siteCanada
- Study dates
- 30 Jul 2023to Mar 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 14 weeks
- All sexes
- Healthy volunteers accepted
- Child
Trials included in our prior systematic review and traditional meta-analysis will be eligible for this IPD meta-analysis if they were registered randomized clinical trials of infants born preterm at less than 29 weeks of gestation and with adequate levels of blinding and allocation concealment. Moreover, eligibility will be restricted to trials conducted in a population of infants born after 2010 receiving contemporary respiratory care, similar to Jensen's cohort within which the severity-based definition of BPD was developed.
The intervention has to involve enteral administration of high-dose DHA supplementation during the neonatal period. A high-dose DHA supplementation is defined as direct enteral DHA supplementation at a dose of at least 40 mg/kg/day or DHA supplementation of breast milk or formula aiming for at least 0.4% of total fatty acids. The intervention should be randomly assigned as either enteral administration of high-dose DHA supplementation OR a control with no or low-dose DHA.
Trials evaluating intravenous DHA interventions or combined interventions (e.g. DHA combined to other nutrients or long-chain polyunsaturated fatty acids) are not considered for inclusion in this IPD meta-analysis to isolate the DHA effects and avoid heterogeneity in the intervention.
The IPD meta-analysis will be conducted using a harmonized severity-based definition of BPD in eligible trials. This definition will be based on Jensen's criteria that adequately predict childhood outcomes in a contemporary cohort of infants born very preterm. To be included, prospectively collected data from eligible trials should allow BPD severity outcome classification and harmonization according to Jensen's severity-based BPD criteria at 36 weeks' PMA.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Enteral Supplementation With High-dose Docosahexaenoic Acid on the Risk for Bronchopulmonary Dysplasia in Very Preterm Infants: A Collaborative Study Protocol for an Individual Participant Data Meta-analysis
This one-stage individual participant data (IPD) meta-analysis study will aim to determine whether high-dose docosahexaenoic acid (DHA) enteral supplementation during the neonatal period is associated with the risk for severe bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (PMA) compared to control, in contemporary cohorts of preterm infants born at less than 29 weeks of gestation. The association between high-dose DHA and severe BPD will also be explored in important subgroups according to sex, gestational age, small-for-gestational age and mode of delivery.
Read the detailed description
Severe BPD is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term neurodevelopmental outcomes, the potential adverse effects of high-dose DHA supplementation on this short-term neonatal morbidity needs further investigations in infants born very preterm.
Therefore, based on previous systematic review findings and a known association between more severe BPD and unfavorable neurodevelopmental outcomes, a deeper understanding of the association between DHA and severe BPD needs further investigations. Harmonization of the severe BPD definition across the recent DHA trials, reclassified according to modern criteria will strengthen the results and allow their interpretation in balance with the potential efficacy of DHA on long-term neurodevelopmental outcomes. Moreover, inconsistent differential responses of DHA on BPD were previously reported according to subgroups such as sex, gestational age and mode of delivery and need to be further explored in this more vulnerable population.
- Being tested
- High-dose DHA, Control
- Keywords
- Omega-3, Fatty acids, Preterm infants, Bronchopulmonary dysplasia, Individual participant data meta-analysis
- Medical subject headings
- Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose DHADietary supplement
Direct enteral DHA supplementation at a dose of at least 40 mg/kg/day or DHA supplementation of breast milk or formula aiming for at least 0.4% of total fatty acids.
ControlDietary supplement
Control with no or low-dose DHA.
| Study group | Role | What they receive |
|---|---|---|
| High-dose DHA | Experimental | Enteral supplementation with high-dose DHA in the neonatal period. Receives: Dietary Supplement: High-dose DHA |
| Control | Placebo comparator | Control. Receives: Dietary Supplement: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severe BPD
A priori defined based on a team consensus, grades of severity (no BPD, grade 1-, 2-, 3-BPD) are defined on the mode of respiratory support at 36 weeks' PMA, regardless of prior or current oxygen therapy according to Jensen's criteria.
Infants will be classified as severe BPD (Yes) if they presented a "grade 2- or 3-BPD" at 36 weeks' PMA, the two most severe grades of BPD according to Jensen's classification. Grade 2 is defined as respiratory support with nasal cannula >2 L/min ("high" flow) or noninvasive positive airway pressure (including nasal intermittent positive pressure ventilation or nasal continuous positive airway pressure). Grade 3 is defined as use of invasive mechanical ventilation.
Infants will be classified as not severe BPD (No) if they presented "no BPD or grade 1-BPD" at 36 weeks' PMA. No BPD is defined as no support. Grade 1 is defined as respiratory support with nasal cannula ≤2 L/min ("low" flow).
Measured: At 36 weeks' PMA
Secondary outcomes (3)
"Grade 2- or 3-BPD or death"
Mortality is defined as death from any cause before 36 weeks' PMA and "Grade 2- or 3-BPD" is defined using Jensen's classification as previously described.
Measured: At 36 weeks' PMA
Severity grades of BPD
Defined as no BPD, grade 1-, 2- or 3-BPD according to Jensen's criteria as previously described.
Measured: At 36 weeks' PMA
Mortality
Defined as death from any cause.
Measured: Up to 36 weeks' PMA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2023
- Study start30 Jul 2023
- Primary completion15 Nov 2023
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary DysplasiaStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,801 participants (actual)
Sponsor and investigators
- Lead sponsor
- CHU de Quebec-Universite Laval
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Laval University, South Australian Health and Medical Research Institute, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Responsible party
- Sponsor
- Investigators
- Isabelle Marc, MD, PhD, Principal investigator, CHU de Québec-Université LavalPascal M. Lavoie, MD, PhD, Principal investigator, University of British ColumbiaAndrew J. McPhee, MB, BS, Principal investigator, South Australian Health and Medical Research InstituteCarmel T. Collins, PhD, Principal investigator, South Australian Health and Medical Research InstituteDavid Simonyan, MSc, Principal investigator, CHU de Québec-Université LavalEtienne Pronovost, BSc, Principal investigator, CHU de Québec-Université LavalMireille Guillot, MD, Principal investigator, CHU de Québec-Université LavalJacqueline F. Gould, PhD, Principal investigator, South Australian Health and Medical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05915806
- Sponsor's protocol ID
- MP-20-2015-2144; F1H-80784
- Status last verified
- Jul 2025
- First submitted
- 30 May 2023
- Last updated
- 14 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There are currently no plan to share IPD obtained during this IPD meta-analysis. However, principal investigators will examine request from any groups for future collaboration.
Publications
Marc I, Boutin A, Pronovost E, Guillot M, Bergeron F, Moore L, Makrides M. High doses of enteral docosahexaenoic acid omega-3 supplementation for prevention of bronchopulmonary dysplasia in very preterm infants: a protocol for a systematic review and meta-analysis. BMJ Open. 2022 Oct 17;12(10):e064515. doi: 10.1136/bmjopen-2022-064515.
PubMed 36253040Marc I, Boutin A, Pronovost E, Perez Herrera NM, Guillot M, Bergeron F, Moore L, Sullivan TR, Lavoie PM, Makrides M. Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review and Meta-analysis. JAMA Netw Open. 2023 Mar 1;6(3):e233934. doi: 10.1001/jamanetworkopen.2023.3934.
PubMed 36943265Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, Kirpalani H, Laughon MM, Poindexter BB, Duncan AF, Yoder BA, Eichenwald EC, DeMauro SB. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Respir Crit Care Med. 2019 Sep 15;200(6):751-759. doi: 10.1164/rccm.201812-2348OC.
PubMed 30995069Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978 Apr;92(4):529-34. doi: 10.1016/s0022-3476(78)80282-0.
PubMed 305471Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF; Trial of Indomethacin Prophylaxis in Preterms (TIPP) Investigators. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003 Mar 5;289(9):1124-9. doi: 10.1001/jama.289.9.1124.
PubMed 12622582Marc I, Lavoie PM, Sullivan TR, Pronovost E, Boutin A, Beltempo M, Guillot M, Gould JF, Simonyan D, McPhee AJ, Mohamed I, Moore L, Makrides M. High-dose docosahexaenoic acid for bronchopulmonary dysplasia severity in very preterm infants: a collaborative individual participant data meta-analysis. Am J Clin Nutr. 2025 Apr;121(4):826-834. doi: 10.1016/j.ajcnut.2025.01.004. Epub 2025 Feb 24.
PubMed 40180500Marc I, Lavoie PM, McPhee AJ, Collins CT, Simonyan D, Pronovost E, Guillot M, Gould JF, Mohamed I, Beltempo M, Boutin A, Fortier I, Sullivan TR, Moore L, Makrides M. Enteral supplementation with high-dose docosahexaenoic acid on the risk of bronchopulmonary dysplasia in very preterm infants: a collaborative study protocol for an individual participant data meta-analysis. BMJ Open. 2023 Jul 30;13(7):e076223. doi: 10.1136/bmjopen-2023-076223.
PubMed 37518076
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enteral Supplementation With High-dose Docosahexaenoic Acid on the Risk for Bronchopulmonary Dysplasia in Very Preterm Infants: A Collaborative Study Protocol for an Individual Participant Data Meta-analysis
- ClinicalTrials.gov ID
- NCT05915806
- Acronym / sponsor ID
- MP-20-2015-2144; F1H-80784
- Keywords
- Omega-3, Fatty acids, Preterm infants, Bronchopulmonary dysplasia, Individual participant data meta-analysis
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,801 participants (actual)
- Lead sponsor
- CHU de Quebec-Universite LavalUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Laval University, South Australian Health and Medical Research Institute, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Study start
- 30 Jul 2023 (actual)
- Primary completion
- 15 Nov 2023 (actual)
- Study completion
- Mar 2026 (estimated)
- First posted
- 23 Jun 2023 (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.
This one-stage individual participant data (IPD) meta-analysis study will aim to determine whether high-dose docosahexaenoic acid (DHA) enteral supplementation during the neonatal period is associated with the risk for severe bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (PMA) compared to control, in contemporary cohorts of preterm infants born at less than 29 weeks of gestation. The association between high-dose DHA and severe BPD will also be explored in important subgroups according to sex, gestational age, small-for-gestational age and mode of delivery.
Detailed description
Severe BPD is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term neurodevelopmental outcomes, the potential adverse effects of high-dose DHA supplementation on this short-term neonatal morbidity needs further investigations in infants born very preterm.
Therefore, based on previous systematic review findings and a known association between more severe BPD and unfavorable neurodevelopmental outcomes, a deeper understanding of the association between DHA and severe BPD needs further investigations. Harmonization of the severe BPD definition across the recent DHA trials, reclassified according to modern criteria will strengthen the results and allow their interpretation in balance with the potential efficacy of DHA on long-term neurodevelopmental outcomes. Moreover, inconsistent differential responses of DHA on BPD were previously reported according to subgroups such as sex, gestational age and mode of delivery and need to be further explored in this more vulnerable population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High-dose DHA | Experimental | Dietary Supplement: High-dose DHAEnteral supplementation with high-dose DHA in the neonatal period. |
| Control | Placebo comparator | Dietary Supplement: ControlControl. |
Who may qualify
- Ages
- Up to 14 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
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 |
|---|---|---|
| High-dose DHADirect enteral DHA supplementation at a dose of at least 40 mg/kg/day or DHA supplementation of breast milk or formula aiming for at least 0.4% of total fatty acids. | Dietary supplement | High-dose DHA |
| ControlControl with no or low-dose DHA. | Dietary supplement | Control |
Primary outcome
Severe BPD
Time frame: At 36 weeks' PMA
A priori defined based on a team consensus, grades of severity (no BPD, grade 1-, 2-, 3-BPD) are defined on the mode of respiratory support at 36 weeks' PMA, regardless of prior or current oxygen therapy according to Jensen's criteria. Infants will be classified as severe BPD (Yes) if they presented a "grade 2- or 3-BPD" at 36 weeks' PMA, the two most severe grades of BPD according to Jensen's classification. Grade 2 is defined as respiratory support with nasal cannula >2 L/min ("high" flow) or noninvasive positive airway pressure (including nasal intermittent positive pressure ventilation or nasal continuous positive airway pressure). Grade 3 is defined as use of invasive mechanical ventilation. Infants will be classified as not severe BPD (No) if they presented "no BPD or grade 1-BPD" at 36 weeks' PMA. No BPD is defined as no support. Grade 1 is defined as respiratory support with nasal cannula ≤2 L/min ("low" flow).
3 secondary outcomes
"Grade 2- or 3-BPD or death"
Time frame: At 36 weeks' PMA
Severity grades of BPD
Time frame: At 36 weeks' PMA
Mortality
Time frame: Up to 36 weeks' PMA
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2025.
- Background: PubMed 36253040Marc I, Boutin A, Pronovost E, Guillot M, Bergeron F, Moore L, Makrides M. High doses of enteral docosahexaenoic acid omega-3 supplementation for prevention of bronchopulmonary dysplasia in very preterm infants: a protocol for a systematic review and meta-analysis. BMJ Open. 2022 Oct 17;12(10):e064515. doi: 10.1136/bmjopen-2022-064515.
- Background: PubMed 36943265Marc I, Boutin A, Pronovost E, Perez Herrera NM, Guillot M, Bergeron F, Moore L, Sullivan TR, Lavoie PM, Makrides M. Association Between Enteral Supplementation With High-Dose Docosahexaenoic Acid and Risk of Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review and Meta-analysis. JAMA Netw Open. 2023 Mar 1;6(3):e233934. doi: 10.1001/jamanetworkopen.2023.3934.
- Background: PubMed 30995069Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, Kirpalani H, Laughon MM, Poindexter BB, Duncan AF, Yoder BA, Eichenwald EC, DeMauro SB. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Respir Crit Care Med. 2019 Sep 15;200(6):751-759. doi: 10.1164/rccm.201812-2348OC.
- Background: PubMed 305471Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978 Apr;92(4):529-34. doi: 10.1016/s0022-3476(78)80282-0.
- Background: PubMed 12622582Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF; Trial of Indomethacin Prophylaxis in Preterms (TIPP) Investigators. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003 Mar 5;289(9):1124-9. doi: 10.1001/jama.289.9.1124.
- Derived from this study: PubMed 40180500Marc I, Lavoie PM, Sullivan TR, Pronovost E, Boutin A, Beltempo M, Guillot M, Gould JF, Simonyan D, McPhee AJ, Mohamed I, Moore L, Makrides M. High-dose docosahexaenoic acid for bronchopulmonary dysplasia severity in very preterm infants: a collaborative individual participant data meta-analysis. Am J Clin Nutr. 2025 Apr;121(4):826-834. doi: 10.1016/j.ajcnut.2025.01.004. Epub 2025 Feb 24.
- Derived from this study: PubMed 37518076Marc I, Lavoie PM, McPhee AJ, Collins CT, Simonyan D, Pronovost E, Guillot M, Gould JF, Mohamed I, Beltempo M, Boutin A, Fortier I, Sullivan TR, Moore L, Makrides M. Enteral supplementation with high-dose docosahexaenoic acid on the risk of bronchopulmonary dysplasia in very preterm infants: a collaborative study protocol for an individual participant data meta-analysis. BMJ Open. 2023 Jul 30;13(7):e076223. doi: 10.1136/bmjopen-2023-076223.
- Individual participant dataSharing planned: No. There are currently no plan to share IPD obtained during this IPD meta-analysis. However, principal investigators will examine request from any groups for future collaboration.
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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.
Isabelle Marc, MD, PhD principal investigator
CHU de Québec-Université Laval
Pascal M. Lavoie, MD, PhD principal investigator
University of British Columbia
Andrew J. McPhee, MB, BS principal investigator
South Australian Health and Medical Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-dose DHA in people with Bronchopulmonary Dysplasia and Child Development, run by CHU de Quebec-Universite Laval at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: under way, not looking for participants, as of the sponsor's last update on 14 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severe BPD (time frame: At 36 weeks' PMA). 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 NCT05915806, which also lists 7 linked publications.
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 14 Jul 2025.