Menu
Recruiting NCT05063149

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

Phase III Interventional Wheezing LRTI Premature

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Broncho-Vaxom, Placebo.
Who it may be relevant to
Registry conditions: Wheezing, LRTI, Premature. Basic parameters: 6 Weeks — 10 Weeks · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Netherlands
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Interventions

  • 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.

Primary outcome measures

  • Total number of physician diagnosed lower RTI and wheezing episodes in the first year of life [Time frame: In the first year of life.]
Secondary outcome measures (11)
  • Time to first lower RTI or wheezing episode [Time frame: In the first and second year of life.]
  • Total number of RTI [Time frame: In the first and second year of life.]
  • Total number of wheezing episodes [Time frame: In the first and second year of life.]
  • Distribution of viruses [Time frame: In the first year of life.]
  • Medication use (bronchodilators, corticosteroids, antibiotics) [Time frame: In the first and second year of life.]
  • Lung function as measured by expiratory variability index (Ventica) [Time frame: In the first year of life.]
  • Quality of life questionnaires [Time frame: In the first and second year of life.]
  • (serious) adverse events [Time frame: In the first year of life.]
  • Serum specific IgE (allergen sensitization) at 12 months [Time frame: At age 12 months]
  • Infant vaccination titers at 12 months [Time frame: At age 12 months]
  • Costs- and cost-effectiveness [Time frame: In the first and second year of life.]

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 (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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Prevention

Study locations

Netherlands · 1 center
  • Franciscus Gasthuis & Vlietland — Rotterdam

Publications

  • Haataja P, Korhonen P, Ojala R, Hirvonen M, Korppi M, Gissler M, Luukkaala T, Tammela O. Hospital admissions for lower respiratory tract infections in children born moderately/late preterm. Pediatr Pulmonol. 2018 Feb;53(2):209-217. doi: 10.1002/ppul.23908. Epub 2017 Nov 29. PMID 29193814
  • Pramana IA, Latzin P, Schlapbach LJ, Hafen G, Kuehni CE, Nelle M, Riedel T, Frey U. Respiratory symptoms in preterm infants: burden of disease in the first year of life. Eur J Med Res. 2011 May 12;16(5):223-30. doi: 10.1186/2047-783x-16-5-223. PMID 21719396
  • Vrijlandt EJ, Kerstjens JM, Duiverman EJ, Bos AF, Reijneveld SA. Moderately preterm children have more respiratory problems during their first 5 years of life than children born full term. Am J Respir Crit Care Med. 2013 Jun 1;187(11):1234-40. doi: 10.1164/rccm.201211-2070OC. PMID 23525931
  • Perez-Yarza EG, Moreno-Galdo A, Ramilo O, Rubi T, Escribano A, Torres A, Sardon O, Oliva C, Perez G, Cortell I, Rovira-Amigo S, Pastor-Vivero MD, Perez-Frias J, Velasco V, Torres-Borrego J, Figuerola J, Barrio MI, Garcia-Hernandez G, Mejias A; SAREPREM 3235 investigators. Risk factors for bronchiolitis, recurrent wheezing, and related hospitalization in preterm infants during the first year of lif PMID 26031206
  • Edwards MO, Kotecha SJ, Lowe J, Richards L, Watkins WJ, Kotecha S. Management of Prematurity-Associated Wheeze and Its Association with Atopy. PLoS One. 2016 May 20;11(5):e0155695. doi: 10.1371/journal.pone.0155695. eCollection 2016. PMID 27203564
  • Kotecha S, Clemm H, Halvorsen T, Kotecha SJ. Bronchial hyper-responsiveness in preterm-born subjects: A systematic review and meta-analysis. Pediatr Allergy Immunol. 2018 Nov;29(7):715-725. doi: 10.1111/pai.12957. Epub 2018 Sep 5. PMID 30014518
  • Moschino L, Carraro S, Baraldi E. Early-life origin and prevention of chronic obstructive pulmonary diseases. Pediatr Allergy Immunol. 2020 Feb;31 Suppl 24:16-18. doi: 10.1111/pai.13157. PMID 32017219
  • Tirone C, Pezza L, Paladini A, Tana M, Aurilia C, Lio A, D'Ippolito S, Tersigni C, Posteraro B, Sanguinetti M, Di Simone N, Vento G. Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes. Front Immunol. 2019 Dec 12;10:2910. doi: 10.3389/fimmu.2019.02910. eCollection 2019. PMID 31921169

Identifiers

NCT: NCT05063149 · NL76165.100.20

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗