Protecting late-moderate preterm infants from respiratory tract infections and wheeze in their first year of life by using bacterial lysates

Phase 3

Not yet recruiting

Conditions: Lower respiratory tract infections and wheezing in moderate-late premature infants

Registration Number: 2024-518498-32-01

Lead Sponsor: Sint Franciscus Vlietland Groep Stichting

Brief Summary: We hypothesize that early education of the neonatal immune system by daily stimulation with microbial elements leads to better protection against lower RTI and subsequent wheezing episodes. It enhances self-initiated antimicrobial immunity by improved and accelerated immune maturation. This will lead to a significant health gain in preterm-born infants with enhanced risk for respiratory diseases.

Moreover, we hypothesize that prolonged bacterial lysate therapy after preterm birth leads to a delay in lower respiratory tract symptoms compared to a shorter treatment. Thus, our main objective is to reduce respiratory tract infections and wheezing in moderate-late preterms in the first years of life by bacterial lysate administration.

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: Authorised, recruitment pending

Sex: Not specified

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 (un-expected in this group); hemodynamic significant cardiac disease; immunodeficiency; severe failure to thrive; birth asphyxia with predicted poor neurological outcome; syn-drome or serious congenital disorder.

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 ex-cipients.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Protea-1: Total number of physician diagnosed lower RTI and wheezing episodes in the first year of life.		Protea-1: Total number of physician diagnosed lower RTI and wheezing episodes in the first year of life.
Protea-2: The time to the first lower respiratory episode after 12 months of age.		Protea-2: The time to the first lower respiratory episode after 12 months of age.

Secondary Outcome Measures

Name	Time	Method
time to first lower RTI or wheezing episode in the first year of life		time to first lower RTI or wheezing episode in the first year of life
total number of RTI in the first and second year of life		total number of RTI in the first and second year of life
total number of wheezing episodes in the first and second year of life		total number of wheezing episodes in the first and second year of life
distribution of viruses during lower RTI/wheezing		distribution of viruses during lower RTI/wheezing
medication use (bronchodilators, corticosteroids, antibiotics)		medication use (bronchodilators, corticosteroids, antibiotics)
lung function as measured by expiratory variability index		lung function as measured by expiratory variability index
quality of life		quality of life
(serious) adverse events (respiratory episodes are not regarded as an (S)AE since they comprise primary and secondary outcomes)		(serious) adverse events (respiratory episodes are not regarded as an (S)AE since they comprise primary and secondary outcomes)
serum specific IgE (allergen sensitization) at 12 months		serum specific IgE (allergen sensitization) at 12 months
infant vaccination titers at 12 months		infant vaccination titers at 12 months
costs- and cost-effectiveness		costs- and cost-effectiveness

Trial Locations

Locations (1): Sint Franciscus Vlietland Groep Stichting
🇳🇱
Rotterdam, Netherlands
Sint Franciscus Vlietland Groep Stichting
🇳🇱Rotterdam, Netherlands
Gerdien Tramper
Site contact
+31104617126
g.tramper@franciscus.nl