Protecting late-moderate preterm infants from respiratory tract infections and wheeze in their first year of life by using bacterial lysates
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Not specified
- Sponsor
- Sint Franciscus Vlietland Groep Stichting
- Enrollment
- 500
- Locations
- 1
- Primary Endpoint
- Protea-1: Total number of physician diagnosed lower RTI and wheezing episodes in the first year of life.
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
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.
Investigators
Research Bureau (Wetenschapsbureau)
Scientific
Sint Franciscus Vlietland Groep Stichting
Eligibility Criteria
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.
Outcomes
Primary Outcomes
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 Outcomes
- 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 wheezing episodes in the first and second year of life
- distribution of viruses during lower RTI/wheezing
- medication use (bronchodilators, corticosteroids, antibiotics)
- lung function as measured by expiratory variability index
- quality of life
- (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
- infant vaccination titers at 12 months
- costs- and cost-effectiveness