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

Phase 3
Recruiting
Conditions
Wheezing
LRTI
Premature
Interventions
Other: Placebo
Registration Number
NCT05063149
Lead Sponsor
Franciscus Gasthuis
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
500
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Broncho-Vaxom treatmentBroncho-VaxomInfants 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.
PlaceboPlaceboInfants in this arm will be given a placebo powder from a capsule that will be indistinguishable from the active study drug.
Primary Outcome Measures
NameTimeMethod
Total number of physician diagnosed lower RTI and wheezing episodes in the first year of lifeIn the first year of life.

Recorded by frequent questionnaires

Secondary Outcome Measures
NameTimeMethod
Lung function as measured by expiratory variability index (Ventica)In the first year of life.

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

Medication use (bronchodilators, corticosteroids, antibiotics)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.

Total number of wheezing episodesIn 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.

Total number of RTIIn 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.

Distribution of virusesIn 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.

Quality of life questionnairesIn the first and second year of life.

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

Serum specific IgE (allergen sensitization) at 12 monthsAt age 12 months

Total IgE and house dust mite specific IgE

Costs- and cost-effectivenessIn the first and second year of life.

Estimated from information from standardized questionnaires

Time to first lower RTI or wheezing episodeIn 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.

(serious) adverse eventsIn 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.

Infant vaccination titers at 12 monthsAt age 12 months

Vaccination titers of haemohilus influenza type B, pneumococci, tetanus

Trial Locations

Locations (1)

Franciscus Gasthuis & Vlietland

🇳🇱

Rotterdam, Zuid-Holland, Netherlands

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