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NCT Number: NCT05063149

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

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.

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Key information

Conditions

Wheezing Female Urogenital Diseases and Pregnancy Complications LRTI Obstetric Labor Complications Obstetric Labor, Premature Pathological Conditions, Signs and Symptoms Pregnancy Complications Premature Premature Birth Respiratory Sounds Signs and Symptoms Signs and Symptoms, Respiratory Urogenital Diseases

Age range

6 week–10 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Franciscus Gasthuis & Vlietland

Rotterdam, South Holland, 3045PM, Netherlands

Location status: Recruiting

Location contact

Inger van Duuren

CONTACT

[email protected]

+31108936169

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Broncho-Vaxom

Drug

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

Other names: OM-85, Broncho-Vaxom concentrate (Bacterial lysate)

Placebo

Other

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

Primary outcomes

  1. Total number of physician diagnosed lower RTI and wheezing episodes in the first year of life

    Time frame: In the first year of life.

    Recorded by frequent questionnaires

Secondary outcomes

  1. Time to first lower RTI or wheezing episode

    Time frame: In the first and second year of life.

    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.

  2. Total number of RTI

    Time frame: In the first and second year of life.

    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.

  3. Total number of wheezing episodes

    Time frame: In the first and second year of life.

    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.

  4. Distribution of viruses

    Time frame: In the first year of life.

    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.

  5. Medication use (bronchodilators, corticosteroids, antibiotics)

    Time frame: In the first and second year of life.

    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.

  6. Lung function as measured by expiratory variability index (Ventica)

    Time frame: In the first year of life.

    Measured at age 6-10 weeks (baseline), 6 months and 12 months in a subset of participants.

  7. Quality of life questionnaires

    Time frame: In the first and second year of life.

    Recorded by extensive questionnaires every six months in the first and second year of life.

  8. (serious) adverse events

    Time frame: In the first year of life.

    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.

  9. Serum specific IgE (allergen sensitization) at 12 months

    Time frame: At age 12 months

    Total IgE and house dust mite specific IgE

  10. Infant vaccination titers at 12 months

    Time frame: At age 12 months

    Vaccination titers of haemohilus influenza type B, pneumococci, tetanus

  11. Costs- and cost-effectiveness

    Time frame: In the first and second year of life.

    Estimated from information from standardized questionnaires

Other outcomes

  1. Gut and respiratory microbiome composition

    Time frame: In the first year of life.

    Measured from faeces and nasofaryngeal swabs taken at age 6-10 weeks, 6 months and 12 months.

  2. Secretory IgA in saliva

    Time frame: In the first year of life

    Saliva will be collected at age 6-10 weeks, 6 months and 12 months.

  3. Immune maturation: immune cells in nasal epithelium

    Time frame: In the first year of life

    Collected by nasal scraping at age 6-10 weeks, 6 months and 12 months. Analysed using masscytometry.

  4. Immune maturation: chemokines and cytokines in nasal lining fluid

    Time frame: In the first year of life

    Collected by nasosorption at age 6-10 weeks, 6 months and 12 months. Analysed using Luminex cyto/chemokine assay.

  5. Immune maturation: immune cells in bloodsamples

    Time frame: In the first year of life

    Collected by blooddraws at age 6-10 weeks, 6 months and 12 months. Analysed using masscytometry.

  6. Serum IgE (total and specific to house dust mite)

    Time frame: At age 12 months

    Measured in blood samples which will be drawn at age 12 months

  7. Immune maturation: Single cell transcriptomics

    Time frame: At age 12 months

    Performed on blood drawn at age 12 months

  8. Whole blood stimulation essays

    Time frame: At age 12 months

    Performed on blood drawn at age 12 months

  9. Biomarkers predictive of high morbidity and/or treatment success

    Time frame: In the first year of life.

    From combined microbial and immunological data

Study contacts

Contact information is provided by the study sponsor or research team.

Inger van Duuren

CONTACT

[email protected]

0031 10 893 61 69

Sponsors and collaborators

Lead sponsor

Franciscus Gasthuis

Other

Collaborators

  • Leiden University Medical Center
  • Maastricht University Medical Center

Registry information

Official study title

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

Acronym: PROTEA

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Sep 30, 2021
Registry last updated
Aug 22, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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