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Late Onset Neonatal SepsisNCT02073214

Effects of Oral Probiotic Supplementation on the Clinical Status of Very-low-birth-weight Preterm Neonates.

A study testing Probiotic in people with Late Onset Neonatal Sepsis and Necrotizing Enterocolitis, run by IBSS Biomed S.A..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study was to evaluate the safety of a probiotic foodstuff and its influence on emergence and development of natural intestinal flora and the clinical status of premature very low birth weight neonates. Read more about this study

Who is it for?
Ages Up to 48 hours
What is being tested?
Probiotic
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
182 participants
Where
No sites listed yet
Study dates
Apr 2012to Dec 2013
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 48 hours
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Infants ≥ 750 g and ≤ 1800 g at birth
  • Gestational age of ≤ 34 weeks
  • Mother's age ≥ 18 years
  • Possibility of feeding by enteral route
  • Possibility of enrolment ≤ 48 hours of age
  • Caucasian race
  • Parent-legal guardian informed consent obtained in writing

Who cannot join

  • Infants < 750 g and > 1800 g at birth
  • Gestational age of > 34 weeks
  • Mother's age < 18 years
  • Contraindicated to enteral nutrition within the first 48 hours of life
  • Birth asphyxia (Apgar score: 0-3)
  • Major congenital abnormalities, including gastrointestinal abnormalities
Show all 14Show fewer
  • Severe clinical condition / disorders which the Investigator considers a contraindication to study participation, including the presence of at least 3 out of 4 of the following symptoms:
  • necessity of mechanical ventilation and FiO2 more than 0.6 elevation to maintain blood oxygen saturation within 88-93%,
  • metabolic acidosis, pH less than 7.20 and BE more than (-10),
  • necessity of vasopressor (antihypotensive) agents to maintain proper arterial blood pressure,
  • signs of damage to at least one vital organ (liver, kidneys, gastrointestinal tract, adrenal glands).
  • Administration of other probiotic preparations
  • Enrolment in any other clinical trial throughout the study period
  • Lack of parent-legal guardian informed consent

About this study

Official title: Effects of Oral Probiotic Supplementation on the Clinical Status of Very-low-birth-weight Preterm Neonates. Multi-centre, Randomised, Double-blind, Placebo-controlled Clinical Study.

The purpose of this study was to evaluate the safety of a probiotic foodstuff and its influence on emergence and development of natural intestinal flora and the clinical status of premature very low birth weight neonates. The study was also intended to investigate reduction of colonisation by pathogenic bacteria and to estimate the incidence of gastrointestinal disorders.

Probotic bacteria contained in the investigational product administered directly after birth are beneficial for the development of normal gut microflora and can prevent or significantly limit gastrointestinal colonisation by pathogenic bacteria and the development of pathogenic flora in a hospital setting. Permanent colonisation with commensal flora in very early life improves gastrointestinal function in premature neonates by reducing the onset of or by decreasing the severity of the signs and symptoms of feeding intolerance and generalised bacterial infections, including sepsis and necrotizing enterocolitis.

Read the detailed description

Neonates defined as having very low birth weight (VLBW) are found to have a number of conditions typical for this period of life and body weight at birth. Perinatal and neonatal infections are relatively common in these babies, which can be attributed to their immunological immaturity (immature cellular or humoral immune responsiveness) and insufficient gastrointestinal tract colonisation by non-pathogenic bacteria, the presence of which depends on the type of delivery, feeding and environment in which the neonates are nursed.

Neonates admitted to neonatal intensive care units, particularly low birth-weight neonates born prematurely or with congenital disorders, are most susceptible. Probiotics administered to neonates are known to compete with pathogenic bacteria for essential nutrients and receptor sites, and to enzymatically modify toxin receptors. They are also known to produce antimicrobial substances, acidify the intestinal environment and stimulate the immune system, helping it reach full maturity. These are the reasons why intestinal microflora normalisation with the help of probiotics can be beneficial for VLBW neonates, especially those requiring intensive medical care.

In a review of clinical studies on the use of probiotics in NEC prevention in neonates, demonstrated beneficial effects of probiotics in a group of VLBW neonates compared to placebo. There are scientific reasons to believe that probiotics administered to neonates modulate the composition of the gut flora colonising the intestinal tract and are beneficial for the development and maturity of the immune system. In hitherto clinical studies, specific probiotic strains were found to provide beneficial effects by limiting infections in the neonatal period, including necrotizing enterocolitis in VLBW neonates.

The purpose of this multicentre, randomized study was to investigate whether the use of a probiotic preparation containing Lactobacillus rhamnosus KL53A and Bifidobacterium breve PB04 influence on emergence and development of natural intestinal flora and the clinical status of premature very low birth weight neonates and reduction of colonisation by pathogenic bacteria and to estimate the incidence of gastrointestinal disorders. The study took place between April 2012 and July 2013 in eight study centres in Poland. It was conducted in accordance with the original protocol and according to ICH-GCP requirements.

The duration of subject's participation in the trial was approximately 49 days, or until they were withdrawn or discharged from the hospital, whichever came earlier, prior to day 49.

As the trial did not concern medicinal product but the foodstuff (food for special medical purpose) it did not require Authority approval but was only subject to relevant Ethics Committee approval.

The study only included neonates who fulfilled the eligibility criteria, after obtaining an informed consent from their parents/legal guardians, to have their baby enrolled in the study and randomized into one of the two study groups: probiotic or placebo. Investigational product were administered during the first 48h of life, at the time of the enteral feed.

Efficacy evaluation was to determine whether the investigational product positively influences the emergence and progressive development of the natural gut flora and the clinical status of preterm VLBW neonates. As part of the efficacy evaluation, it was also examined whether the probiotic agent has the capacity to inhibit pathogenic colonisation and to reduce the incidence of gastrointestinal disorders, as compared to placebo.

Safety was evaluated by determining whether investigational product in VLBW preterm neonates increases AE/SAE incidence and influences the type of adverse events and serious adverse events as compared to placebo.

Being tested
Probiotic, Placebo
Medical subject headings
Neonatal Sepsis, Enterocolitis, Necrotizing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ProbioticOther

    Also called Food for special medical purposes

    Standard treatment plus probiotic

  • PlaceboOther

    Standard treatment plus placebo

Study groups in NCT02073214
Study groupRoleWhat they receive
ProbioticExperimentalSingle dose of probiotic, was administered enterally twice daily with food (in the morning and in the evening). The first dose of probiotic was administered within the first 48 hours after birth. The probiotic administration was continued for 6 weeks or until hospital discharge (whichever was earlier). Discontinuation of the enteral nutrition was equivalent with discontinuation of the administration of the probiotic. If the probiotic was discontinued for more than 7 days, the patient was withdrawn from the study.
Receives: Other: Probiotic
PlaceboPlacebo comparatorSingle dose of placebo was administered enterally twice daily with food (in the morning and in the evening). The first dose of placebo was administered within the first 48 hours after birth. The placebo administration was continued for 6 weeks or until hospital discharge (whichever was earlier). Discontinuation of the enteral nutrition was equivalent with discontinuation of the administration of the placebo. If the placebo was discontinued for more than 7 days, the patient was withdrawn from the study.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Gastrointestinal tract colonisation

    Bacteriological tests involved quantitative and qualitative assessment of neonatal gut flora during clinical follow-up. Bacterial populations of Lactobacillus and Bifidobacterium as well as pathogenic bacteria were assesed.

    Stool samples were collected at 7-day intervals (±2 days) in the period of investigational product intake, and on Day 7 (±2 days) after the last dose of the investigational product.

    Measured: Assesed on days 1, 7, 14, 21, 28, 35, 42 and 49 (assesed weekly within eight weeks)

  2. Feeding intolerance episodes (including: gastric residuals, vomiting, regurgitation of food, abdominal distension, abdominal rigidity, gut motility disorders)

    Clinical parameters were evaluated throughout the period of care according to standard neonatal care procedures.

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

  3. Incidence and type of adverse events and serious adverse events with special regard to sepsis caused by bacteria contained in investigational product.

    Safety was evaluated by determining whether investigational product in VLBW preterm neonates increases AE/SAE incidence and influences the type of adverse events and serious adverse events as compared to placebo with special regard to sepsis caused by bacteria contained in investigational product .

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

Secondary outcomes (9)
  1. Late onset sepsis caused by Gram positive or Gram negative bacteria

    Sepsis was confirmed by positive blood cultures. Clinical parameters were evaluated throughout the period of care according to standard neonatal care procedures.

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

  2. Gastrointestinal perforation

    Clinical parameters were evaluated throughout the period of care according to standard neonatal care procedures.

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

  3. Duration of total parenteral nutrition (days)

    Duration of total parenteral nutrition (hyperalimentation) was evaluated until full enteral nutrition is restored.

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

  4. Duration (days) of absence of enteral nutrition due to gastrointestinal disorders

    Clinical parameters were evaluated throughout the period of care according to standard neonatal care procedures.

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

  5. Duration (days) of absence of enteral nutrition for reasons other than gastrointestinal disorders

    Clinical parameters were evaluated throughout the period of care according to standard neonatal care procedures.

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

  6. Weight, length and head circumference

    Weight, length and head circumference were evaluated throughout the period of care according to standard neonatal care procedures.

    Measured: Weight was measured once daily, head circumference was measured once a week, and body length was measured on Day 1 and on Day 7 (±2 days) from the last dose (or until the patient was discharged or withdrawn from the study)

  7. NEC - intensity and severity

    Severity of neonatal necrotizing enterocolitis was determined according Bell's criteria. Clinical parameters were evaluated throughout the period of care according to standard neonatal care procedures.

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

  8. Mortality rate, with a focus on deaths attributed to NEC and sepsis

    Clinical parameters were evaluated throughout the period of care according to standard neonatal care procedures.

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

  9. Duration of hospitalization (days) (until discharge)

    Duration of hospitalization was investigated from the date of patient enrolment until discharge.

    Measured: Assesed on a daily basis (from 1 to 42 and on day 49)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Feb 2014 (estimated)
  2. Study startApr 2012
  3. Primary completionJul 2013
  4. Study completionDec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
182 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02073214
Sponsor's protocol ID
PB-DM/SBK-NEC-01/11
Status last verified
Feb 2014
First submitted
25 Feb 2014
Last updated
27 Feb 2014
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A study testing Probiotic in people with Late Onset Neonatal Sepsis and Necrotizing Enterocolitis, run by IBSS Biomed S.A..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Gastrointestinal tract colonisation (time frame: Assesed on days 1, 7, 14, 21, 28, 35, 42 and 49 (assesed weekly within eight weeks)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2014.

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