Acute Otitis MediaNCT03516409
Bio-Kult Infantis® in AAD Prevention in Infants
A study testing Biokult in people with Acute Otitis Media, run by Probiotics International Ltd. at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 35 monthsHealthy volunteers can take part
- Conditions the study is for
- Acute Otitis Media
- What is being tested?
- Biokult
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 276 participants
- Where
- 1 siteItaly
- Study dates
- 18 Apr 2018to 15 Dec 2018
- 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 6 to 35 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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:
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- 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).
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Hospital "Sandro Pertini"
Roma, Italia, 00157
Salvatore Tripodi, Dr
About this study
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
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.
Read more
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.
- Conditions
- Acute Otitis Media
- Being tested
- Biokult, Placebo
- Keywords
- probiotics, prebiotics, diarrhoea
- Medical subject headings
- Otitis Media, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiokultDietary supplement
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
PlaceboDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Bio-Kult Infantis | Active comparator | 1 sachet once a day mixed with milk, water or food. Receives: Dietary Supplement: Biokult |
| Placebo | Placebo comparator | 1 sachet once a day mixed with milk, water or food. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: day 10
Secondary outcomes (13)
Incidence of AAD
occurrence or non-occurrence of AAD according to time frame
Measured: Days 24 and 38
Duration of AAD
Frequency (frequency of the occurrences as mean) of AAD according to time frame
Measured: Days 10, 24 and 38
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
Measured: from end of antibiotic treatment to Day 2, and from Day 24 to Day 38
Mean stool frequency
Frequency of evacuations (frequency of the occurrences per 24 hours)
Measured: Days 10, 24 and 38
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
Measured: Days 10, 24 and 38
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
Measured: Day 38
Rate of resolution of AOM
frequency of occurrences (resolution of AOM) as mean according to time frame
Measured: Days 10, 24 and 38
Rate of residual middle-ear effusion (fluid behind the tympanic membrane)
frequency of occurrences (residual middle-ear effusion) as mean according to time frame
Measured: Days 10, 24 and 38
Rate of AOM relapse
frequency of occurrences (AOM relapse) as mean according to time frame
Measured: Days 24 and 38
Dermatitis in the diaper area (diaper rash)
occurrence / or non-occurrence of dermatitis according to time frame
Measured: Days 10, 24 and 38
Rate of interruption of antibiotic therapy
occurrence / or non-occurrence according to time frame
Measured: Day 10
Use of acetaminophen (as rescue medication)
Use of acetaminophen according to time frame
Measured: Day 38
Evaluation of product palatability
palatability valuated by parents / legal guardians by means of a VAS according to time frame
Measured: Day 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2018
- Study start18 Apr 2018
- Primary completion15 Dec 2018 (estimated)
- Study completion15 Dec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Otitis MediaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Treatment groups: 6 - 35 months old. * Bio-Kult Infantis * Placebo (maltodextrine DE19)
- Masking
- None (open label)
- Enrolment
- 276 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Probiotics International Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sprim Advanced Life Sciences
- Responsible party
- Sponsor
- Investigators
- Salvatore Tripodi, Dr, Principal investigator, UOC pediatria Hospital "Sandro Pertini"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03516409
- Sponsor's protocol ID
- AAD_BKI_001
- Status last verified
- Sep 2018
- First submitted
- 19 Apr 2018
- Last updated
- 12 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03516409
- Acronym / sponsor ID
- AAD_BKI_001
- Conditions
- Acute Otitis Media
- Keywords
- probiotics, prebiotics, diarrhoea
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 276 participants (estimated)
- Lead sponsor
- Probiotics International Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Sprim Advanced Life Sciences
- Study start
- 18 Apr 2018 (actual)
- Primary completion
- 15 Dec 2018 (estimated)
- Study completion
- 15 Dec 2018 (estimated)
- First posted
- 4 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Treatment groups: 6 - 35 months old. * Bio-Kult Infantis * Placebo (maltodextrine DE19)
| Arm | Type | Receives |
|---|---|---|
| Bio-Kult Infantis | Active comparator | Dietary Supplement: Biokult1 sachet once a day mixed with milk, water or food. |
| Placebo | Placebo comparator | Dietary Supplement: Placebo1 sachet once a day mixed with milk, water or food. |
Who may qualify
- Ages
- 6 to 35 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BiokultBio-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 | Dietary supplement | Bio-Kult Infantis |
| PlaceboIP 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. | Dietary supplement | Placebo |
Primary outcome
Incidence of AAD
Time frame: day 10
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
13 secondary outcomes
Incidence of AAD
Time frame: Days 24 and 38
Duration of AAD
Time frame: Days 10, 24 and 38
Mean stool consistency during antibiotic treatment
Time frame: from end of antibiotic treatment to Day 2, and from Day 24 to Day 38
Mean stool frequency
Time frame: Days 10, 24 and 38
Incidence and mean frequency of abdominal pain, nausea, vomiting, bloating, and appetite suppression
Time frame: Days 10, 24 and 38
Time to resolution of AOM
Time frame: Day 38
Rate of resolution of AOM
Time frame: Days 10, 24 and 38
Rate of residual middle-ear effusion (fluid behind the tympanic membrane)
Time frame: Days 10, 24 and 38
Rate of AOM relapse
Time frame: Days 24 and 38
Dermatitis in the diaper area (diaper rash)
Time frame: Days 10, 24 and 38
Rate of interruption of antibiotic therapy
Time frame: Day 10
Use of acetaminophen (as rescue medication)
Time frame: Day 38
Evaluation of product palatability
Time frame: Day 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Salvatore Tripodi, Dr principal investigator
UOC pediatria Hospital "Sandro Pertini"
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Biokult in people with Acute Otitis Media, run by Probiotics International Ltd. at 1 site in Italy.
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 10 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 12 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ashton Harper, Dr. (+44 7712 321 033, Ashton.Harper@protexin.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of AAD (time frame: day 10). 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 12 Sep 2018.