Protecting Preterm Infants From Respiratory Tract Infections and Wheeze by Using Bacterial Lysates.

Premature Clinical Trial

— PROTEA  

Official title:

Protecting Late-moderate Preterm Infants From Respiratory Tract Infections and Wheeze in Their First Year of Life by Using Bacterial Lysates.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05063149
• Other study ID #: NL76165.100.20
• Status: Recruiting
• Phase: Phase 3
• Start date: January 18, 2022
• Est. completion date: December 2026

Study information

• Verified date: February 2024
• Source: Franciscus Gasthuis
• Contact: Inger van Duuren
• Phone: 0031 10 893 61 69
• Email: proteastudie[@]franciscus.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

This is a randomised placebo-controlled trial including 500 otherwise healthy moderate-late preterm infants. Participants will receive bacterial lysate (Broncho-Vaxom, 3,5mg) or placebo powder for ten days each month, from 6 weeks after birth until 12 moths of age. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Weeks to 10 Weeks

Eligibility

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.

Related Conditions & MeSH terms

• LRTI
• Premature
• Respiratory Sounds
• Respiratory Tract Infections
• Wheezing

Intervention

Drug:
• Broncho-Vaxom
Broncho-Vaxom is a bacterial extract comprising lyophilised fractions of 21 different inactivated bacterial strains, which are frequently causing RTI.

Other:
• Placebo
Placebo powder from a capsule will be given, which will be indistinguishable from the active study drug.

Locations

Country	Name	City	State
Netherlands	Franciscus Gasthuis & Vlietland	Rotterdam	Zuid-Holland

Sponsors (3)

Lead Sponsor	Collaborator
Franciscus Gasthuis	Leiden University Medical Center, Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (45)

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* Note: There are 45 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gut and respiratory microbiome composition	Measured from faeces and nasofaryngeal swabs taken at age 6-10 weeks, 6 months and 12 months.	In the first year of life.
Other	Secretory IgA in saliva	Saliva will be collected at age 6-10 weeks, 6 months and 12 months.	In the first year of life
Other	Immune maturation: immune cells in nasal epithelium	Collected by nasal scraping at age 6-10 weeks, 6 months and 12 months. Analysed using masscytometry.	In the first year of life
Other	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.	In the first year of life
Other	Immune maturation: immune cells in bloodsamples	Collected by blooddraws at age 6-10 weeks, 6 months and 12 months. Analysed using masscytometry.	In the first year of life
Other	Serum IgE (total and specific to house dust mite)	Measured in blood samples which will be drawn at age 12 months	At age 12 months
Other	Immune maturation: Single cell transcriptomics	Performed on blood drawn at age 12 months	At age 12 months
Other	Whole blood stimulation essays	Performed on blood drawn at age 12 months	At age 12 months
Other	Biomarkers predictive of high morbidity and/or treatment success	From combined microbial and immunological data	In the first year of life.
Primary	Total number of physician diagnosed lower RTI and wheezing episodes in the first year of life	Recorded by frequent questionnaires	In the first year of life.
Secondary	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.	In the first and second year of life.
Secondary	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.	In the first and second year of life.
Secondary	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.	In the first and second year of life.
Secondary	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.	In the first year of life.
Secondary	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.	In the first and second year of life.
Secondary	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.	In the first year of life.
Secondary	Quality of life questionnaires	Recorded by extensive questionnaires every six months in the first and second year of life.	In the first and second year of life.
Secondary	(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.	In the first year of life.
Secondary	Serum specific IgE (allergen sensitization) at 12 months	Total IgE and house dust mite specific IgE	At age 12 months
Secondary	Infant vaccination titers at 12 months	Vaccination titers of haemohilus influenza type B, pneumococci, tetanus	At age 12 months
Secondary	Costs- and cost-effectiveness	Estimated from information from standardized questionnaires	In the first and second year of life.