Back to resultsBio-Kult Infantis® in AAD Prevention in Infants
Primary Purpose
Acute Otitis Media
Status
Unknown status
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Biokult
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Otitis Media focused on measuring probiotics, prebiotics, diarrhoea
Eligibility Criteria
Inclusion Criteria:
- 1. Parents / legal guardians signed written informed consent to participate in the study.
- 2. Male and female infants aged 6 - 35 months (6 and 35 inclusive).
- 3. Infants eligible to receive co-amoxiclav to treat AOM according to current Italian guidelines, edited by Società Italiana di Pediatria, 2012.
- 4. Outpatients infants (not hospitalized).
- 5. Infants who have received at least 2 doses of pneumococcal conjugate vaccine.
6. Infants diagnosed with Acute Otitis Media (AOM) based on the following three criteria:
- onset, within the preceding 48 hours, of symptoms that parents or legal guardians rated with a score of at least 3 on the Acute Otitis Media Severity of Symptoms (AOM - SOS);
- presence of middle-ear effusion;
- moderate or marked bulging of the tympanic membrane or slight bulging accompanied by either otalgia or marked erythema of the membrane
- 7. Infants already exposed to formula milk without Cow Milk Protein Allergy (CMPA) (not requiring a formal diagnosis of CMPA).
Exclusion Criteria:
- 1. Infants with any other acute illness apart from AOM (e.g. pneumonia) or with any other chronic illness (e.g. cystic fibrosis).
- 2. Infants with a clinical history positive for any allergy or intolerance to amoxicillin, clavulanic acid or any component of the active product, the placebo or of the rescue medication (acetaminophen).
- 3. Infants presenting contraindications to the study products, to co-amoxiclav or to the rescue medication, according to concerning Summaries of Product Characteristics (SPC).
- 4. Infants being treated with any drug whose pharmacokinetics can interfere with the intake of amoxicillin, clavulanic acid, the study products or the rescue medication or with any drug with which amoxicillin, clavulanic acid, the study products or the rescue medication can interact, according to concerning Summaries of Product Characteristics (SPC).
- 5. Infants with a clinical history positive for allergy to any other antibiotics.
- 6. Infants who have received antibiotics within 8 weeks prior to enrollment.
- 7. Infants who have had otalgia for longer than 48 hours or perforation of the tympanic membrane.
- 8. Infants suffering from active diarrhoea at time of enrollment or chronic diarrhoea.
- 9. Infants who consumed a probiotic product for medicinal purposes within 7 days prior to enrollment.
- 10. Unwillingness on the part of the parents or legal guardians to interrupt any regular intake of other probiotics during the study period
- 11. Diagnosis of Clostridium difficile-associated diarrhoea (CDAD) within the previous three months from enrolment
Sites / Locations
- Hospital "Sandro Pertini"Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Bio-Kult Infantis
Placebo
Arm Description
1 sachet once a day mixed with milk, water or food.
1 sachet once a day mixed with milk, water or food.
Outcomes
Primary Outcome Measures
Incidence of AAD
occurrence or non-occurrence of AAD according to time frame. An occurrence of AAD is defined as 3 or more watery stools in 1 day or 2 watery stools daily for at least 2 days
Secondary Outcome Measures
Incidence of AAD
occurrence or non-occurrence of AAD according to time frame
Duration of AAD
Frequency (frequency of the occurrences as mean) of AAD according to time frame
Mean stool consistency during antibiotic treatment
Stool consistency evaluated according to the validated Infatl Stool Scale; mean values will be considered according to time frame
Mean stool frequency
Frequency of evacuations (frequency of the occurrences per 24 hours)
Incidence and mean frequency of abdominal pain, nausea, vomiting, bloating, and appetite suppression
Occurrence or non-occurrence and frequency of occurrences as mean according to time frame
Time to resolution of AOM
Time (Days) to the first recording of an Acute Otitis Media Severity of Symptoms score (AOM-SOS Score) of 0 and 1 and the time to the second of two successive recordings of that score according to time frame
Rate of resolution of AOM
frequency of occurrences (resolution of AOM) as mean according to time frame
Rate of residual middle-ear effusion (fluid behind the tympanic membrane)
frequency of occurrences (residual middle-ear effusion) as mean according to time frame
Rate of AOM relapse
frequency of occurrences (AOM relapse) as mean according to time frame
Dermatitis in the diaper area (diaper rash)
occurrence / or non-occurrence of dermatitis according to time frame
Rate of interruption of antibiotic therapy
occurrence / or non-occurrence according to time frame
Use of acetaminophen (as rescue medication)
Use of acetaminophen according to time frame
Evaluation of product palatability
palatability valuated by parents / legal guardians by means of a VAS according to time frame
Full Information
NCT ID
NCT03516409
First Posted
April 19, 2018
Last Updated
September 11, 2018
Sponsor
Probiotics International Ltd.
Collaborators
Sprim Advanced Life Sciences
1. Study Identification
Unique Protocol Identification Number
NCT03516409
Brief Title
Bio-Kult Infantis® in AAD Prevention in Infants
Official Title
Efficacy of a Synbiotic Product (Probiotics + Prebiotics) in the Prevention of Antibiotics-associated Diarrhoea (AAD) in Infants. A Multicenter, Double Blind, Parallel Group, Placebo Controlled, Randomized Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Unknown status
Study Start Date
April 18, 2018 (Actual)
Primary Completion Date
December 15, 2018 (Anticipated)
Study Completion Date
December 15, 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Probiotics International Ltd.
Collaborators
Sprim Advanced Life Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Background: antibiotic-associated diarrhoea (AAD) is defined as an acute inflammation of the intestinal mucosa associated to the administration of antibiotics. Its aetiology seems to be linked to the impact of antibiotics on the normal digestive microbiota. Acute otitis media (AOM) is a common paediatric condition and it is one of the most commonly cited indication for antimicrobial therapy in children (amoxicillin + clavulanic acid).
Treatment modalities for AAD are limited because no established treatment exists for non-Clostridium difficile associated AAD, except for discontinuing antibiotic therapy. Measures to prevent AAD include the use of probiotics. The rationale for the use of probiotics in AAD assumes that, considering the pathogenesis of AAD, AAD is associated with disturbance in the normal intestinal microbiota; administrating specific probiotic strains it is possible to normalize unbalanced indigenous microbiota.
Scientific evidence suggests that prebiotics could be beneficial too. Prebiotics can act in synergy with probiotics, being efficacious in suppressing the growth of pathogenic bacteria that may occur during antibiotic therapy.
Study rationale: the principal side effects of treatment with amoxicillin-clavulanate include diarrhoea, vomiting and allergic reactions. Aim of this study is to evaluate the effectiveness of the administration of a synbiotic product, Bio-Kult Infantis®, in the prevention of AAD during a standard therapy with amoxicillin-clavulanate to treat AOM.
Objective: to evaluate the effectiveness of a synbiotic product in the prevention of Antibiotics-Associated Diarrhoea (AAD) during a concomitant standard therapy with amoxicillin / clavulanic acid, also known as co-amoxiclav, to treat Acute Otitis Media (AOM).
Study design: this is a multicenter, double blind, parallel group, placebo controlled, randomized clinical study. 276 children 6 - 35 months old will be enrolled and then randomized into one of the two study groups (Bio-Kult Infantis® + co-amoxiclav standard treatment for AOM / placebo + co-amoxiclav standard treatment for AOM). A comparison will be performed to evaluate the effectiveness of a synbiotic product in the prevention of AAD during the concomitant standard therapy with co-amoxiclav.
During the study 4 visits will have to be performed at the study centre, and extra visits will be performed in case of AOM relapse after recovery. The study will last for each patient 38 ± 6 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Otitis Media
Keywords
probiotics, prebiotics, diarrhoea
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Treatment groups: 6 - 35 months old.
Bio-Kult Infantis
Placebo (maltodextrine DE19)
Masking
None (Open Label)
Masking Description
A multicenter, double blind, parallel group, placebo controlled, randomized study.
Allocation
Randomized
Enrollment
276 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Bio-Kult Infantis
Arm Type
Active Comparator
Arm Description
1 sachet once a day mixed with milk, water or food.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
1 sachet once a day mixed with milk, water or food.
Intervention Type
Dietary Supplement
Intervention Name(s)
Biokult
Intervention Description
Bio-Kult Infantis® is a multi-strain formula containing a probiotic formulation comprising 7 strains of probiotics, high content of Omega-3, Vitamin D3 and Preplex® (50% FOS and 50% gum acacia).
Each sachet contains:
Minimum 1 billion microorganisms per sachet (1 x 109CFU/g), guaranteed throughout the shelf life
DHA + EPA: >1mg per sachet
Vitamin D3: 2.5mcg per sachet (50% of Nutrient Reference Value). Bio-Kult Infantis® presents itself in the form of a white powder, packaged in sachets of 1 g each
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
IP placebo is manufactured so to contain maltodextrin DE19 and have the same organoleptic properties of the active product (similar to the study product in appearance and taste) but without active ingredient. It contains 100% maltodextrin DE19.
Moreover, placebo sachets are equal in color, shape and weight (1 g) to IP sachets.
Primary Outcome Measure Information:
Title
Incidence of AAD
Description
occurrence or non-occurrence of AAD according to time frame. An occurrence of AAD is defined as 3 or more watery stools in 1 day or 2 watery stools daily for at least 2 days
Time Frame
day 10
Secondary Outcome Measure Information:
Title
Incidence of AAD
Description
occurrence or non-occurrence of AAD according to time frame
Time Frame
Days 24 and 38
Title
Duration of AAD
Description
Frequency (frequency of the occurrences as mean) of AAD according to time frame
Time Frame
Days 10, 24 and 38
Title
Mean stool consistency during antibiotic treatment
Description
Stool consistency evaluated according to the validated Infatl Stool Scale; mean values will be considered according to time frame
Time Frame
from end of antibiotic treatment to Day 2, and from Day 24 to Day 38
Title
Mean stool frequency
Description
Frequency of evacuations (frequency of the occurrences per 24 hours)
Time Frame
Days 10, 24 and 38
Title
Incidence and mean frequency of abdominal pain, nausea, vomiting, bloating, and appetite suppression
Description
Occurrence or non-occurrence and frequency of occurrences as mean according to time frame
Time Frame
Days 10, 24 and 38
Title
Time to resolution of AOM
Description
Time (Days) to the first recording of an Acute Otitis Media Severity of Symptoms score (AOM-SOS Score) of 0 and 1 and the time to the second of two successive recordings of that score according to time frame
Time Frame
Day 38
Title
Rate of resolution of AOM
Description
frequency of occurrences (resolution of AOM) as mean according to time frame
Time Frame
Days 10, 24 and 38
Title
Rate of residual middle-ear effusion (fluid behind the tympanic membrane)
Description
frequency of occurrences (residual middle-ear effusion) as mean according to time frame
Time Frame
Days 10, 24 and 38
Title
Rate of AOM relapse
Description
frequency of occurrences (AOM relapse) as mean according to time frame
Time Frame
Days 24 and 38
Title
Dermatitis in the diaper area (diaper rash)
Description
occurrence / or non-occurrence of dermatitis according to time frame
Time Frame
Days 10, 24 and 38
Title
Rate of interruption of antibiotic therapy
Description
occurrence / or non-occurrence according to time frame
Time Frame
Day 10
Title
Use of acetaminophen (as rescue medication)
Description
Use of acetaminophen according to time frame
Time Frame
Day 38
Title
Evaluation of product palatability
Description
palatability valuated by parents / legal guardians by means of a VAS according to time frame
Time Frame
Day 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
35 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
1. Parents / legal guardians signed written informed consent to participate in the study.
2. Male and female infants aged 6 - 35 months (6 and 35 inclusive).
3. Infants eligible to receive co-amoxiclav to treat AOM according to current Italian guidelines, edited by Società Italiana di Pediatria, 2012.
4. Outpatients infants (not hospitalized).
5. Infants who have received at least 2 doses of pneumococcal conjugate vaccine.
6. Infants diagnosed with Acute Otitis Media (AOM) based on the following three criteria:
onset, within the preceding 48 hours, of symptoms that parents or legal guardians rated with a score of at least 3 on the Acute Otitis Media Severity of Symptoms (AOM - SOS);
presence of middle-ear effusion;
moderate or marked bulging of the tympanic membrane or slight bulging accompanied by either otalgia or marked erythema of the membrane
7. Infants already exposed to formula milk without Cow Milk Protein Allergy (CMPA) (not requiring a formal diagnosis of CMPA).
Exclusion Criteria:
1. Infants with any other acute illness apart from AOM (e.g. pneumonia) or with any other chronic illness (e.g. cystic fibrosis).
2. Infants with a clinical history positive for any allergy or intolerance to amoxicillin, clavulanic acid or any component of the active product, the placebo or of the rescue medication (acetaminophen).
3. Infants presenting contraindications to the study products, to co-amoxiclav or to the rescue medication, according to concerning Summaries of Product Characteristics (SPC).
4. Infants being treated with any drug whose pharmacokinetics can interfere with the intake of amoxicillin, clavulanic acid, the study products or the rescue medication or with any drug with which amoxicillin, clavulanic acid, the study products or the rescue medication can interact, according to concerning Summaries of Product Characteristics (SPC).
5. Infants with a clinical history positive for allergy to any other antibiotics.
6. Infants who have received antibiotics within 8 weeks prior to enrollment.
7. Infants who have had otalgia for longer than 48 hours or perforation of the tympanic membrane.
8. Infants suffering from active diarrhoea at time of enrollment or chronic diarrhoea.
9. Infants who consumed a probiotic product for medicinal purposes within 7 days prior to enrollment.
10. Unwillingness on the part of the parents or legal guardians to interrupt any regular intake of other probiotics during the study period
11. Diagnosis of Clostridium difficile-associated diarrhoea (CDAD) within the previous three months from enrolment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ashton Harper, Dr.
Phone
+44 7712 321 033
Email
Ashton.Harper@protexin.com
First Name & Middle Initial & Last Name or Official Title & Degree
Cesare Mutti, Dr
Phone
+390245495838
Email
cesare.mutti@sprim.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Salvatore Tripodi, Dr
Organizational Affiliation
UOC pediatria Hospital "Sandro Pertini"
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital "Sandro Pertini"
City
Roma
State/Province
Italia
ZIP/Postal Code
00157
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salvatore Tripodi, Dr
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Bio-Kult Infantis® in AAD Prevention in Infants
We'll reach out to this number within 24 hrs