A Phase 3 interventional study of Broncho-Vaxom and Placebo in Wheezing, LRTI and Premature, sponsored by Franciscus Gasthuis. Recruiting at 1 site in Netherlands. Open to participants aged 6 Weeks to 10 Weeks. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by Franciscus Gasthuis · Phase 3, Interventional, and Prevention
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.
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.
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.
Exclusion Criteria:
Infants in this arm will be given 3,5mg bacterial lysate (OM-85) 10 days per month from 6 weeks after birth until 12 months of age. At age 12 months they will be (if informed consent for Protea-2 is provided) randomised over Broncho-Vaxom treatment and placebo again.
Drug: Broncho-Vaxom
Infants in this arm will be given a placebo powder from a capsule that will be indistinguishable from the active study drug.
Other: Placebo
Broncho-Vaxom is a bacterial extract comprising lyophilised fractions of 21 different inactivated bacterial strains, which are frequently causing RTI.
Also known as: OM-85, Broncho-Vaxom concentrate (Bacterial lysate)
Placebo powder from a capsule will be given, which will be indistinguishable from the active study drug.
Total number of physician diagnosed lower RTI and wheezing episodes in the first year of life
Recorded by frequent questionnaires
Time frame: In the first year of life.
Time to first lower RTI or wheezing episode
Recorded by short weekly questionnaires (which will be filled in during the first year of life) and more extensive questionnaires every six months in the first and second year of life.
Time frame: In the first and second year of life.
Total number of RTI
Recorded by short weekly questionnaires (which will be filled in during the first year of life) and more extensive questionnaires every six months in the first and second year of life.
Time frame: In the first and second year of life.
Total number of wheezing episodes
Recorded by short weekly questionnaires (which will be filled in during the first year of life) and more extensive questionnaires every six months in the first and second year of life.
Time frame: In the first and second year of life.
Distribution of viruses
Viruses present in the nasofarynx during complaints of lower respiratory tract infection or wheezing. Nasofaryngeal swabs will be taken in case of complaints during the first year of life. In the second year of life this will not be done.
Time frame: In the first year of life.
Medication use (bronchodilators, corticosteroids, antibiotics)
Recorded by short weekly questionnaires (which will be filled in during the first year of life) and more extensive questionnaires every six months in the first and second year of life.
Time frame: In the first and second year of life.
Lung function as measured by expiratory variability index (Ventica)
Measured at age 6-10 weeks (baseline), 6 months and 12 months in a subset of participants.
Time frame: In the first year of life.
Quality of life questionnaires
Recorded by extensive questionnaires every six months in the first and second year of life.
Time frame: In the first and second year of life.
(serious) adverse events
Will be reported by parents immediately. Respiratory episodes are not regarded as an (S)AE since these episodes comprise primary and secondary outcomes. (S)AE's are only expected in the first year of life because the treatment stops at the age of 12 months.
Time frame: In the first year of life.
Serum specific IgE (allergen sensitization) at 12 months
Total IgE and house dust mite specific IgE
Time frame: At age 12 months
Infant vaccination titers at 12 months
Vaccination titers of haemohilus influenza type B, pneumococci, tetanus
Time frame: At age 12 months
Costs- and cost-effectiveness
Estimated from information from standardized questionnaires
Time frame: In the first and second year of life.
Gut and respiratory microbiome composition
Measured from faeces and nasofaryngeal swabs taken at age 6-10 weeks, 6 months and 12 months.
Time frame: In the first year of life.
Secretory IgA in saliva or nasal lining fluid
Saliva will be collected at age 6-10 weeks, 6 months and 12 months.
Time frame: In the first year of life
Immune maturation: immune cells in nasal epithelium
Collected by nasal scraping at age 6-10 weeks, 6 months and 12 months. Analysed using masscytometry.
Time frame: In the first year of life
Immune maturation: chemokines and cytokines in nasal lining fluid
Collected by nasosorption at age 6-10 weeks, 6 months and 12 months. Analysed using Luminex cyto/chemokine assay.
Time frame: In the first year of life
Immune maturation: immune cells in bloodsamples
Collected by blooddraws at age 6-10 weeks, 6 months and 12 months. Analysed using masscytometry.
Time frame: In the first year of life
Serum IgE (total and specific to house dust mite)
Measured in blood samples which will be drawn at age 12 months
Time frame: At age 12 months
Immune maturation: Single cell transcriptomics
Performed on blood drawn at age 12 months
Time frame: At age 12 months
Whole blood stimulation essays
Performed on blood drawn at age 12 months
Time frame: At age 12 months
Biomarkers predictive of high morbidity and/or treatment success
From combined microbial and immunological data
Time frame: In the first year of life.
Plan to share: Yes — Researchdata will be shared in data repositories according to the FAIR principle. Clinical data about respiratory health will be shared in the DANS repository. Inlcuding metadata which will ensure reusability. Sequencing data will be shared online in the ENA repository which will provide an unique global identifier. All used bioinformatics pipelines for data analysis will be made accessible on a GitHub account. Immunological data will be shared in NCBI Gene Expression omnibus and ImmPort. Used analysis pipelines for the transcriptomics data will also be tracked and can be shared using a Github account. All data shared will be pneudonymized.
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Franciscus Gasthuis