Clinical trial NCT02802059: E. Coli Nissle 1917 - Suspension for Infection Prophylaxis
Official title: E. Coli Nissle 1917 - Suspension for Infection Prophylaxis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections
Lead sponsor: Ardeypharm GmbH
Sponsor class: INDUSTRY
Collaborators: name: ICON plc
name: Clinscience Sp. z o.o.
First posted: 2016-06-16
Enrollment: 567
Sex: ALL
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study evaluates the long term effects of E. coli strain Nissle 1917 (EcN-Suspension) probiotic bacteria administration on the number of both, bacterial and viral infections during the first 24 months of infant's life. Half of study participants will receive EcN-Suspension, while the other half will receive placebo. In an additional non-clinical explorative evaluation will furthermore be investigated whether the early intestinal colonization with E.coli strain Nissle 1917 affects the establishment of the intestinal microbiota.

Detailed description: In the course of the present trial the participants will be observed during the first 24 months of life, starting right after birth.

All newborns meeting all inclusion criteria and non-fulfilling any exclusion criteria will be included into the trial. Each participant of this clinical trial will be randomly allocated to one of the two trial arms, by using the method of randomly permuted blocks.

The newborns will be primarily treated during the first three weeks of life and re-treated after 6 and 12 months according to trial interventional plan.

Data on the efficacy and safety will be recorded during control visits after first month, 6, 12, 18 and 24 months.

A follow-up examination of study participants will be performed two years after the end of the participation in the present trial (i.e. at an age of 48 months), during which each child will be examined for its normal physical and cognitive development (covered by the U8 standardized examination). In addition data on allergic/atopic complaints or symptoms will be recorded.

In an additional non-clinical explorative evaluation, it will furthermore be investigated whether the early intestinal colonization with E.coli strain Nissle 1917 affects the establishment of the intestinal microbiota. Therefore stool samples of study participants will be collected at an age of 24 and 48 months. The microbial composition of these samples will be characterized and compared between the two trial arms (EcN vs. placebo).

Eligibility criteria: Inclusion Criteria:

* Signed informed consent form by the parents
* Age at inclusion: max. 120 hours after birth
* Functionally mature infant
* Gestational age more than 35th week of development
* Mother's intention to breastfeed the participant
* Readiness of the mother to administer no probiotics additionally to the trial medication

Exclusion Criteria:

* Non-fulfilment of the at least one inclusion criteria
* Lack of propensity/compliance of mother
* 5 min APGAR SCORE less than 5
* 10 min APGAR SCORE less than 8
* pH of umbilical cord blood less than 7 (Determination not obligatory, if APGAR SCORES do not indicate that the child may have suffered from a perinatal asphyxia)
* Any perinatal infection required antibiotic treatment
* Birth weight less than 2000 g
* TORCH-infection of the mother
* HIV-infection of the mother
* Any severe medical condition of mother or newborn which in the opinion of the investigator may have a critical impact on the conduct of the study.

Primary outcomes:
measure: Number of infections
timeFrame: during the first 24 months of life
Secondary outcomes:
measure: Severity of the course of infections considered as primary variables quantified as the "duration of infections"
timeFrame: during the first 24 months of infants' life
measure: Severity of the course of infections considered as primary variables quantified as the "number of hospital admissions caused by infections"
timeFrame: during the first 24 months of infants' life
measure: Severity of the course of infections considered as primary variables quantified as the "mean number of in-hospital spent days due to infections"
timeFrame: during the first 24 months of infants' life
measure: Severity of the course of infections considered as primary variables quantified as the "number of antibiotic treatments due to infections".
timeFrame: during the first 24 months of infants' life
measure: Severity of the course of infections considered as primary variables quantified as the "number of adverse events".
timeFrame: during the first 24 months of infants' life
measure: Severity of the course of infections considered as primary variables quantified as the "tolerance to trial medication".
timeFrame: during the first 24 months of infants' life
Other outcomes:
Locations:
city: Halle (Saale)
country: Germany
facility: Krankenhaus St. Elisabeth & St. Barbara
city: Jena
country: Germany
facility: Universitätsklinikum Jena - Klinik für Kinder- und Jugendmedizin
city: Potsdam
country: Germany
facility: Klinikum Westbrandenburg
city: Rostock
country: Germany
facility: Klinikum Südstadt Rostock - Abteilung für Neonatologie
city: Bydgoszcz
country: Poland
facility: Oddział Kliniczny Noworodków, Wcześniaków z Intensywną Terapią Noworodka wraz z Wyjazdowym Zespołem "N"
city: Warsaw
country: Poland
facility: Samodzielny Publiczny Dziecięcy Szpital Kliniczny Oddział Kliniczny Neonatologiiul
Study officials:
affiliation: Ardeypharm GmbH
name: Corinna Wolff, Dipl-Biophys
role: STUDY_DIRECTOR
affiliation: Klinikum Südstadt Rostock - Abteilung für Neonatologie
name: Dirk M Olbertz, MD
role: PRINCIPAL_INVESTIGATOR
References: