Clinical trial NCT05063149: Protecting Preterm Infants From Respiratory Tract Infections and Wheeze by Using Bacterial Lysates.
Official title: Protecting Late-moderate Preterm Infants From Respiratory Tract Infections and Wheeze in Their First Years of Life by Using Bacterial Lysates.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Wheezing
LRTI
Premature
Lead sponsor: Franciscus Gasthuis
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
name: Maastricht University Medical Center
First posted: 2021-09-30
Enrollment: 500
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Half of the participants (250) will receive treatment (Broncho-Vaxom) and the other half will receive placebo. Randomization will be stratified for gestational age (moderate (30+0-32+6) vs. late (33+0-35+6) prematurity). In the follow-up study Protea-2, infants from the treatment arm in year 1 will be randomised to receive Broncho-Vaxom or placebo in year 2. Randomisation will stratified for gestational age again, but also for the amount of lower respiratory episodes in year 1 (\<2 vs. \>/=2) Infants from the control arm in year 1 will not receive treatment in year 2.
Primary purpose: PREVENTION

Brief summary: The primary objective of this study is to reduce respiratory tract infections and wheezing in moderate-late preterms in the first years of life by bacterial lysate administration. Next to determine the correlation of biological markers with respiratory symptoms, immune protection and treatment effect.

Detailed description: This is a randomised placebo-controlled trial including 500 otherwise healthy moderate-late preterm infants. Participants will receive bacterial lysate (OM-85/Broncho-Vaxom, 3,5mg) or placebo powder for ten days each month, from 6-10 weeks after birth until 12 months after birth. At 12 months, parents of participants are asked to join in Protea-2. If they do, participants in the treatment arm of year 1 are randomised again over placebo and OM-85 and treated until the age of 24 months. Clinical data will be continuously collected by e-Health and 3 (possibly digital) study visits; with optional biological sampling and lung function at baseline, 6 and 12 months. And in case of participation in Protea-2 also at 24 months.

Main study parameters are doctor diagnosed lower RTI and wheezing episodes in the first year of life. Biological sampling will allow investigation of immune maturation, as well as microbiome development in the respiratory tract and gut. Also, biomarkers for risk-group selection and/or treatment success will be examined.

Eligibility criteria: Inclusion Criteria:

* Gestational age at delivery between 30+0 and 35+6 weeks
* Postnatal age at least 6 weeks at randomization \& postmenstrual age at least 37 weeks
* Written informed consent by both parents or formal caregivers

Exclusion Criteria:

* Underlying other severe respiratory disease such as broncho-pulmonary dysplasia (unexpected in this group); hemodynamic significant cardiac disease; immunodefi-ciency; severe failure to thrive; birth asphyxia with predicted poor neurological out-come; syndrome or serious congenital disorder.
* Lower RTI before randomization
* Dysmaturity and/or weight \< 2.5 kg at age of randomization.
* Maternal TNF-alpha inhibitors or other immunosuppression during pregnancy and/or breastfeeding
* Parents unable to speak and read Dutch/English language
* Known allergic hypersensitivity to the active ingredients/substance or to any of the excipients.

Primary outcomes:
measure: Total number of physician diagnosed lower RTI and wheezing episodes in the first year of life
timeFrame: In the first year of life.
Secondary outcomes:
measure: Time to first lower RTI or wheezing episode
timeFrame: In the first and second year of life.
measure: Total number of RTI
timeFrame: In the first and second year of life.
measure: Total number of wheezing episodes
timeFrame: In the first and second year of life.
measure: Distribution of viruses
timeFrame: In the first year of life.
measure: Medication use (bronchodilators, corticosteroids, antibiotics)
timeFrame: In the first and second year of life.
measure: Lung function as measured by expiratory variability index (Ventica)
timeFrame: In the first year of life.
measure: Quality of life questionnaires
timeFrame: In the first and second year of life.
measure: (serious) adverse events
timeFrame: In the first year of life.
measure: Serum specific IgE (allergen sensitization) at 12 months
timeFrame: At age 12 months
measure: Infant vaccination titers at 12 months
timeFrame: At age 12 months
measure: Costs- and cost-effectiveness
timeFrame: In the first and second year of life.
Other outcomes:
measure: Gut and respiratory microbiome composition
timeFrame: In the first year of life.
measure: Secretory IgA in saliva
timeFrame: In the first year of life
measure: Immune maturation: immune cells in nasal epithelium
timeFrame: In the first year of life
measure: Immune maturation: chemokines and cytokines in nasal lining fluid
timeFrame: In the first year of life
measure: Immune maturation: immune cells in bloodsamples
timeFrame: In the first year of life
measure: Serum IgE (total and specific to house dust mite)
timeFrame: At age 12 months
measure: Immune maturation: Single cell transcriptomics
timeFrame: At age 12 months
measure: Whole blood stimulation essays
timeFrame: At age 12 months
measure: Biomarkers predictive of high morbidity and/or treatment success
timeFrame: In the first year of life.
Locations:
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
state: Zuid-Holland
Study officials:
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