Helping Underdeveloped Lungs with Cells (HULC)-2 Mesenchymal Stromal Cells in extreme preterm infants at risk of developing Bronchopulmonary Dysplasia – A Phase 2 Multi-Centre Double Blind Randomized Controlled Trial Study Protocol
Bibliographic record
Abstract
Abstract Introduction Bronchopulmonary dysplasia (BPD) remains a major complication among extremely low gestational age (ELGA) infants, with long-term respiratory and neurodevelopmental consequences. Despite advances in neonatal care, effective therapies to prevent BPD are lacking. Mesenchymal stromal cells (MSC), particularly those derived from umbilical cord (UC-MSC), offer promise due to their pleiotropic effects. Preclinical and early-phase clinical studies have demonstrated safety and potential efficacy of MSC in neonatal lung injury. The HULC-2 trial aims to evaluate whether multiple intravenous doses of human allogenic UC-MSC can reduce mechanical ventilation duration and improve the respiratory outcome in ELGA infants at high risk of developing BPD. Methods and Analysis HULC-2 is a multicenter, double-blind, randomized controlled Phase II trial conducted in Canadian Neonatal Intensive Care Units. ELGA infants (gestational age <28 weeks) who remain ventilator-dependent between 4–14 days of life will be randomized to receive either three weekly intravenous doses of UC-MSC (10×10^6 cells/kg/dose) or a sham procedure. The primary outcome is ventilation-free days (VFDs) at 120 days post-randomization, accounting for mortality. Secondary outcomes include cell administration safety, respiratory and neurodevelopmental outcomes, and complications of prematurity. A total of 168 participants will be enrolled to detect a clinically meaningful difference in VFDs. Ethics and Dissemination Ethics approval has been obtained, and the trial is registered on ClinicalTrials.gov. Results will be disseminated via peer-reviewed publications, conferences, and public engagement platforms. Parent partners are actively involved in study design and dissemination to ensure relevance and transparency. Strengths and limitations of this study Ventilation-free day (VFD) is a clinically relevant primary outcome compared to BPD, as prolonged mechanical ventilation in preterm infants is directly associated with increased risks of mortality, neurodevelopmental impairment, and other complications, making VFDs a more sensitive and meaningful measure of both survival and recovery Use of a multiple-dose regimen and fresh cell product to optimize the cell’s therapeutic potential Cell product was tested in a large animal model of BPD Parents’ involvement in the trial design and development to deliver meaningful research that benefits patients and increase study acceptance among parents. A sham procedure was chosen over a placebo based on parent feedback, which increased the risk of unblinding, but strategies to mitigate that risk were developed.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.006 |
| Meta-epidemiology (narrow) | 0.004 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.019 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".