Clinical Research Directory

Heterologous Cord Blood-Derived Red Blood Cell for Transfusion in Extremely Preterm Infants

Anemia is a condition in which there are not enough red blood cells to carry oxygen throughout the body. It is very common in extremely preterm infants (born before 28 weeks of pregnancy), and many of these babies require red blood cell transfusions during their hospital stay. Currently, transfusions are given using red blood cells donated by adults. An alternative option is to use red blood cells collected from umbilical cord blood, which may be more similar to a newborn's own blood. This approach has been used in some neonatal units with encouraging results and no reported safety concerns. This study aims to determine whether transfusion with umbilical cord blood improves clinical outcomes and reduces potential side effects compared to standard adult donor blood transfusion in extremely preterm infants. We hypothesize that umbilical cord blood transfusion will be at least as safe as adult donor blood and may provide clinical benefits. About 115 extremely preterm infants admitted to neonatal units in Catalonia will participate. If parents agree, their baby will be randomly assigned to receive either compatible umbilical cord blood or compatible adult donor blood if a transfusion becomes necessary. Babies will only receive a transfusion if they clinically need one. If cord blood is not available at the time of transfusion, the baby will receive compatible adult donor blood regardless of the assigned group. To evaluate the response to treatment, small blood samples will be collected at birth, at one month of life, and 24 hours after any transfusion. These samples are taken at the same times as routine blood tests, so participation does not require additional needle sticks. The amount of blood collected is minimal (about 0.2 mL per sample). In addition, a painless and non-invasive sensor will be placed on the baby's head for 24 hours to measure oxygen delivery to the brain. Urine samples will also be collected before and after transfusion to help assess how oxygen reaches body tissues. Participation will continue until the baby reaches 36 weeks of postmenstrual age or is discharged from the hospital, whichever comes first.

Impact of the Early Life Virome Development on Bronchopulmonary Dysplasia in Preterm Neonates

Bronchopulmonary dysplasia (BPD) is the most frequent respiratory complication in extremely preterm infants. It leads to significant mortality and long-term morbidity. The pathophysiology of BPD is multifactorial, involving inflammation and oxidative stress due to neonatal exposures such as mechanical ventilation and infections. Previous studies have highlighted the role of respiratory bacterial microbiota in BPD development, with causal effects having been demonstrated in murine models. Moreover, the gut-lung axis is implicated in BPD, with alterations to the gut bacteriome and mycobiome observed in preterm infants in the first weeks of life who later develop BPD. Despite its critical role in shaping immunity and microbial ecology, the virome has been largely understudied in preterm infants. Our recent observations have revealed the existence of a detectable respiratory virome at birth in most very preterm infants, and certain virome and bacteriome profiles have been found to be associated with different risks of developing BPD. Hypothesis: The early acquisition and dynamics of the respiratory and gut virome in the first weeks of life influence microbiome structure and pulmonary immune development, contributing to BPD pathogenesis. These dynamics may define distinct endotypes of BPD with implications for prognosis and therapy. Objectives: * Primary: Characterize the evolution of the respiratory and gut virome during the first 3 weeks of life in infants born \<30 weeks of gestation, comparing those who develop BPD to those who do not. * Secondary: * Define different BPD endotypes and assess their association with demographic and clinical characteristics * Characterise the structure of the microbiome within each endotype. * Compare the evolution of the virome, bacteriome and mycobiome within and between anatomical sites. Study Design: A monocentric, prospective observational cohort of 40 preterm infants (\<30 weeks GA) requiring respiratory support at birth. Infants are classified at 36 weeks' postmenstrual age (PMA) into BPD and non-BPD groups based on oxygen dependency. Sample Collection: * Oropharyngeal aspirates: Collected at days 0, 7, 14, and 21. * Stool samples: Collected at days 7, 14, and 21. Methods: * Virome analysis: Viral metagenomics * Metatranscriptomics: Assess transcriptionally active bacteria/fungi and host gene expression. * Data integration: Multi-omics factor analysis and unsupervised clustering to identify BPD endotypes; ecological network analysis to evaluate microbiome structure and interactions. Outcomes: * Primary: Qualitative and quantitative assessment of virome composition and diversity, including dynamics and persistence across timepoints. * Secondary: Definition of microbiome-based endotypes; interaction networks between viruses, bacteria, and fungi; and longitudinal comparisons of microbial diversity and composition across anatomical sites.

PK, Safety and Preliminary Efficacy Study of Montelukast in Critically Ill Infants With Developing Bronchopulmonary Dysplasia

The purpose of the study is to learn how safe montelukast may be in premature infants at significant risk for Bronchopulmonary Dysplasia (BPD) and to determine how much and how quickly montelukast moves from the stomach into the bloodstream, and how quickly it is removed from the bloodstream. Data supporting the prospect of montelukast benefit involved 6 previous studies involving 206 preterm infants. The dosing ranged from 0.5 to 2.5 mg/kg/day, which aligns with the proposed initial dose of 0.75 mg/kg/day. Though each previous study had a small population, collectively they reveal montelukast as a promising drug in populations of preterm infants developing BPD and for individual preterm infants who are "developing BPD." Thus, researchers expect clinical benefit for preterm infants in this study. Despite the benefit-to-risk ratio presented by these previous studies, the optimal dose remains to be determined; thus, this study design and PK analysis will start with the lowest dose that is likely to provide direct benefit to participants.

Can Betamethasone Given After Birth Help Extremely Premature Babies Come Off Breathing Support Safely and Effectively?

The goal of this study is to determine if giving a steroid medication (specifically, betamethasone) after birth can help extremely premature babies (born before 28 weeks) come off breathing machines safely and reduce their risk of chronic lung disease associated with prematurity. Only babies who meet treatment criteria will receive this medication. Babies who do not meet treatment criteria will not receive medication. The main questions it aims to answer are: * Does betamethasone make it easier for babies to come off a breathing machine? * Does betamethasone cause any harmful side effects on growth or development? All babies in this study will: * Receive standard NICU care, with or without betamethasone * Have their progress, growth, and development followed over time

Characterization of Extracellular Vesicles From the Cord Blood of Extremely Preterm New Borns and Their Correlation With Severe Morbidity and Mortality

This study aims to understand the role of extracellular vesicles (EVs) in extremely premature infants, those born before 28 weeks of gestation. EVs are tiny particles released by cells that carry important information about the body's condition. In extremely premature infants, blood vessels may not function properly, leading to serious health problems such as bleeding in the brain, lung injury, or severe infections. Researchers believe that analyzing EVs in the umbilical cord blood of these infants may help predict which babies are at higher risk of developing these complications. By studying the size, number, and type of EVs, the team hopes to identify early markers that can guide doctors in providing better care. The study will collect cord blood from 30 eligible infants born at the CHU of Montpellier. Blood samples will be processed to isolate platelet-poor plasma, which contains EVs. This plasma will be stored in a biobank, allowing future research on EVs and their role in extreme prematurity. EVs will then be analyzed in the laboratory to assess their characteristics and any links to severe health issues. The findings from this study could improve understanding of circulatory problems in extremely premature infants, help identify early predictors of severe complications, and inform better monitoring and treatment strategies. The creation of a plasma biobank also provides a valuable resource for future research to enhance care and outcomes for this vulnerable population.

Continued Pressure for Alveolar Protection (CPAP Trial)

The objective of the CPAP Trial is to test whether extending CPAP until 34 weeks' PMA or for at least 2 additional weeks compared to weaning to a nasal canula will decrease the likelihood of bronchopulmonary dysplasia or death at 36 weeks' PMA.

National Surveillance and Prevention of Neonatal VAP

The goal of this observational study is to improve how hospital-acquired lung infections (called ventilator-associated pneumonia, or VAP) are diagnosed, treated and prevented in very low birth weight (VLBW) infants, babies born very early (preterm) or very small who often require respiratory support in hospital's neonatal intensive care units (NICUs). The main questions it aims to answer are: * How often do very-low-birth-weight (VLBW) infants get ventilator-associated pneumonia (VAP) in hospitals across Canada? * How often are these VAP infections caused by germs that are resistant to antimicrobials (also known as antimicrobial-resistant organisms or AROs)? * What types of antimicrobial-resistant germs (AROs) are causing them? * How are these infections being treated with antibiotics, and can we reduce unnecessary antibiotic use? * Which diagnostic definition is the best and most accurate for diagnosing VAP in newborns, based on real patient data and expert agreement? * Can we use this information to create clear, evidence-based guidelines that help hospitals prevent and treat VAP in the same, effective way? Researchers will compare how different hospitals define, report, and manage VAP to devise a shared, evidence-based approach that will lead to more accurate diagnoses and better treatment and outcomes for neonatal VAP. Researchers will: * Use data already collected in hospital records (per existing standard of clinical care). * Analyse how often VAP occurs, how it is diagnosed, and how it is treated * Work with experts and hospitals to develop and implement a standard, evidence-based plan for diagnosing, managing and preventing VAP in newborns The overarching goal is to create a clear, nationwide approach to ensure hospitals across Canada care for preterm babies in a standardized manner, reduce infection rates, avoid unnecessary antibiotic use, and improve outcomes for these vulnerable infants.

Combined Oscillation-Volume guarantEe Study

Respiratory Distress Syndrome (RDS) remains the most common respiratory complication in the early postnatal period among preterm infants born before 32 weeks' gestational age. For this population, implementing lung-protective ventilation strategies is essential to shorten the duration of intubation, reduce the incidence and severity of bronchopulmonary dysplasia (BPD), lower mortality, and improve overall outcomes. HFOV-VG was first reported in 2015 to be safely applied in neonates. The fundamental principle lies in its ability to stabilize the tidal volume of high-frequency ventilation (VThf), thereby reducing sheer stress from amplitude fluctuations, while simultaneously permitting lower VThf settings to minimize volutrauma. This study aims to evaluate whether HFOV+VG is superior to HFOV in reducing the composite outcome of grade 2-3 BPD or death at 36 weeks' post-menstrual age (PMA).

The Budesonide in Babies (BiB) Trial

This is a Phase 3, randomized, masked, active-controlled, multicenter trial designed to determine whether early intratracheal administration of a combination of budesonide with surfactant, as compared to surfactant alone, will reduce the incidence of physiologic bronchopulmonary dysplasia (BPD) or death by 36 weeks' post-menstrual age in extremely preterm infants.

Metformin for Premature Infants With Bronchopulmonary Dysplasia

The overall objective of this study is to investigate the role of metformin in decreasing lung injury and promoting lung growth in premature infants. There are two phases to this pilot study. For Phase 0, the goal is to investigate the safety and tolerance of oral metformin in premature who have been diagnosed with bronchopulmonary dysplasia (BPD) at 36-44 weeks gestation. For Phase 1, the goal is to investigate metformin safety and tolerance in extremely premature infants who are 7-30 days old who have an increased risk of BPD. The main questions it aims to answer are: * how well do older premature infants tolerate metformin? * how well do younger premature infants tolerate metformin?

Dexamethasone Regimens for BPD Prevention in Preterm Infants

The goal of this clinical trial is to compare the effectiveness of two different dexamethasone treatment regimens (the DART regimen and the medium-dose tapering regimen) in reducing the incidence of Bronchopulmonary Dysplasia (BPD) or death by 36 weeks of postmenstrual age in premature infants. This study will also assess the safety of these treatments. The main questions it aims to answer are: Does the DART regimen, compared to the medium-dose tapering regimen, lower the rate of BPD or BPD-related death by 36 weeks of postmenstrual age in eligible premature infants? How do the two regimens compare in terms of short-term respiratory outcomes (like time to come off the ventilator), complications at hospital discharge, and long-term neurodevelopmental outcomes at 18-24 months of corrected age? Researchers will compare the DART regimen group (lower cumulative dose, given over 10 days) to the medium-dose tapering regimen group (higher cumulative dose, given over 7 days) to see which one is more effective and safer. Participants will: Inclusion Criteria (Must meet ALL of the following) 1. Gestational age 24+0 to 29+6 weeks; requires invasive mechanical ventilation for ≥14 days after birth; within 14-28 days of age at first receive of dexamethasone. 2. FiO₂ \> 40% and MAP \> 8 cmH₂O (maintained for at least 24 hours prior to enrollment). 3. Parent/Legal guardian has provided signed informed consent. 4. No use of other steroid medications prior to enrollment, as explicitly stated in the inclusion criteria. 2\. Exclusion Criteria (Will be excluded if they meet ANY of the following) 1. Presence of ventilator-associated pneumonia at the time of enrollment. 2. Severe congenital malformations (e.g., severe cardiac anomalies, congenital diaphragmatic hernia, etc.), or known immunodeficiency. 3. Suffering from other severe life-threatening illnesses with a short-expected survival time. 4. Parent/Legal guardian refuses to participate in the study.

Long-Term Burden of BPD and Health-Related Quality of Life (BronQ Family)

The objective of this study is to examine the long-term impact of having a child with Bronchopulmonary Dysplasia (BPD) on the parents and caregivers from the time of diagnosis through adulthood. The primary focus will be on parents and caregivers of children until the age of 18 (\< 18) years who were diagnosed with BPD as newborns. Data will be collected through an online questionnaire in France, Germany, Italy, the Netherlands, Spain, the United Kingdom (including Northern Ireland), and the United States. It will ask about inclusion and exclusion criteria, background information (caregiver, child, and family situation), the child's medical situation, parental health-related quality of life (HRQoL), health literacy, feelings, support structures, and economic burden of the family.

The Correlation Between Red Cell Transfusion and Complications of Prematurity

The aim of this clinical trial is to learn if there is a correlation between the erythrocyte transfusion in the early neonatal period in premature infants and early and late complications of prematurity. The main questions it aims to answer are: * Do premature infants who receive blood transfusions within their first month of life have a higher risk of early prematurity complications, such as retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and intraventricular haemorrhage? * Do premature infants who receive blood transfusions during their first month of life have worse neurological and neurodevelopmental outcomes than those who do not? The first part of the study is retrospective, using data collected from participants' histories. The second part is prospective, evaluating neurological and neurodevelopmental outcomes at the age of six years.

Mesenchymal Stromal Cell Therapy to Prevent Bronchopulmonary Dysplasia in Extreme Preterm Infants

This clinical trial aims to evaluate the safety and efficacy of mesenchymal stromal cell (MSC) therapy in extreme preterm infants to prevent bronchopulmonary dysplasia, the main respiratory complication of preterm birth. Study participants will receive either multiple intravenous doses (total of 3 doses) of MSC derived from human donor umbilical cord tissue (intervention group) or no uc-MSC injection (control group) to confirm the safety of IV MSC in extreme preterm infants and evaluate the potential benefit of MSC therapy on their respiratory health as well as on other complications related to preterm birth.

Chloride Imbalance in Preterm Infants

In adults and children low or high blood chloride levels are linked to the risk of death. The aim of this observational study is to determine whether there is a relationship between low or high blood chloride levels and the risk of death or long-term lung problems. We will also learn the risk factors and associated conditions of high or low blood chloride levels. We will include infants born before 32 weeks of pregnancy or have a birth weight of less than 1500 grams in the study. The main question it aims to answer is: Is there a relationship between low or high blood chloride levels in the first 4-6 weeks of life and risk of death or long-term lung problems in premature babies? We will examine the medical reports of babies who were followed up in neonatal intensive care unit over the past 5 years.

Overview: Use of Respiratory Support At Home in Children

the primary outcome is to describe the perceived success of the use of the respiratory support from the parent's point of view

Enhancing Lung Health in Kids With Structural Lung Damage and Malformations: Azithromycin (AZI) for Airway Infection Prevention

Children with lung and airway malformations or early structural lung damage face significant challenges, often leading to recurrent respiratory infections, hospitalizations, and decreased quality of life. Despite various interventions, effective strategies are urgently needed. The link between these conditions and persistent bacterial bronchitis remains unclear, possibly due to compromised airways and reduced mucociliary clearance. Although antibiotics can alleviate symptoms, relapse is common. Experts often prescribe prophylactic azithromycin, despite limited evidence of its benefits. Azithromycin shows promise due to its anti-inflammatory and immunomodulatory effects but lacks thorough evaluation in this population. To address this gap, we propose a double-blind, randomized controlled trial to assess azithromycin's effectiveness and safety in preventing respiratory infections in children with these conditions. This research aims to inform clinical practice and improve the health of affected children and their families.