Efficacy and Safety of Sinquanon for Prevention of Antibiotic-associated Diarrhea in Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of a probiotic, SINQUANON, on the reduction of the occurrence of diarrhea associated with antibiotic use in adults.

Detailed Description
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The study aims to evaluate the efficacy of a specialized multi-strain probiotic, SINQUANON, on the reduction of the incidence of antibiotic-associated diarrhea in adults and to demonstrate the benefit of administering the specialized multi-strain probiotic as a routine add-on to antibiotic therapy on prevention of antibiotic-associated diarrhea in adults who take antibiotics in the outpatient setting.

Official Title
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Phase 4, Efficacy and Safety of Sinquanon for Prevention of Antibiotic-associated Diarrhea in Adults in the Out-patient Setting: Prospective, Multicenter, Double-blind, Placebo-controlled Randomized Parallel-arm Clinical Study

Conditions
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Antibiotic-associated Diarrhea

Intervention / Treatment
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* Dietary Supplement: Sinquanon
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject aged 18 to 60 years. The subject has given written informed consent after being provided orally with information about the study objective and design, including the administration regimen of the studied probiotic and the study procedures, the available safety data, as well as the rights and obligations of a participant. The subject initiates oral antibiotic treatment in the ambulatory setting. Acceptable antibiotic therapy: Broad-spectrum penicillins Cephalosporins Quinolones Tetracyclines Sequential administration of two antibiotics from the allowed groups is permitted, if the total duration of the antibiotic treatment does not exceed 10 days. Planned duration of the antibiotic treatment of 5 to 10 days. Body mass index (BMI) of 18.0 to 29.9 kg/m2 In the opinion of the Investigator, the subject can adhere to the visit schedule, to be compliant with the trial treatment regimen and to complete the study. The patient has a smartphone and can use it. Exclusion Criteria: Antibiotics use within 60 days prior to randomization. Daily consumption of probiotics, yogurt with probiotics and inability to stop this consumption. Use of antidiarrheal medications, laxatives, enemas, or suppositories within 1 week prior to randomization and for the duration of the trial. An episode of diarrhea within 30 days before screening, defined as ≥3 loose or liquid stools over 24 hours, regardless of the cause of the diarrhea. Acute or chronic constipation - average number of formed stools <3 per week. Allergy or hypersensitivity to any of the ingredients of the trial product. Allergy or hypersensitivity to the antibiotic prescribed on Day 1. Prior documented infection with Clostridioides difficile ≤3 months before screening. History of chronic gastrointestinal conditions, including irritable bowel syndrome, chronic constipation, chronic diarrhea, dyspepsia, gastroesophageal reflux disease, diverticulitis, ulcerative colitis, Crohn's disease or any other abnormality in the absorption or gastrointestinal dysfunction. Use of proton-pump inhibitors (PPIs) within 30 days prior to Day 1 and for the duration of the study. Surgery to the intestines, artificial heart valve, history of rheumatological heart disease or infectious endocarditis within one year prior to screening. Immunosuppressive therapy or any condition causing immunosuppression (including hematologic malignancies, AIDS, long-lasting corticosteroid treatment). Planned administration of antibiotics, different from those acceptable for the study. Patients in severe condition requiring urgent hospitalization or planned hospitalization during the study. Planned administration of antibiotics >10 days. BMI ≥ 30 kg/m2. Pregnant or lactating women; women who plan to get pregnant during the study. Drug abuse or alcohol within the past year. Unstable medical conditions, in the judgement of the Investigator. Eating disorders (for example, anorexia, bulimia). On a vegan diet. Participation in a clinical trial within 60 days prior to randomization. Inability to comply with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, multicenter, double-blind, placebo-controlled, randomized, parallel-arm clinical study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>During the antibiotic dosing (from 5 to 10 days): 2 capsules once a day 2 hours before or 2 hours after antibiotic administration. 14 days following completion of antibiotic dosing: 1 capsule a day. | Dietary Supplement: Sinquanon<br>* This probiotic food supplement includes fourteen probiotic bacterial strains of Lactobacillus Spp, Bifidobacterium Spp., Bacillus coagulans, Saccharomyces boulardii, three prebiotics and Vitamin-B complex - B1, B2, B3, B6, B7, B9 in an enterosolvent cellulose capsule. The product includes supplementary substances: maltodextrin and magnesium stearate. 2 capsules once a day during the antibiotic dosing. 1 capsule a day for 14 days following completion of antibiotic dosing.<br>|
| Placebo Comparator: Placebo<br>During the antibiotic dosing (from 5 to 10 days): 2 capsules once a day 2 hours before or 2 hours after antibiotic administration. 14 days following completion of antibiotic dosing: 1 capsule a day. | Dietary Supplement: Placebo<br>* The placebo product will have the same appearance as the active product and the same composition but without the live bacteria, prebiotics, and vitamin-B complex. 2 capsules once a day during the antibiotic dosing. 1 capsule a day for 14 days following completion of antibiotic dosing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Antibiotic-Associated diarrhea (AAD) | The incidence of AAD is defined as the number of subjects who experience at least one day of diarrhea compared to the total number of subjects enrolled in the given treatment arm. AAD is defined as 3 or more loose or liquid stools (types 5-7 according to Bristol Stool Scale [BSS]) over a period of 24 hours. | By 21+2 days after completion of antibiotic dosing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of AAD | Investigator will assess AAD severity using the following modified scale defining AAD as: severe: ≥7 unformed/loose/liquid stools; moderate: 5-6 unformed/loose/liquid stools; mild: a change in the stool pattern 3-4 unformed/loose/liquid stools a day. Investigator's assessment will take into consideration the 24-hour period presenting with the worst severity. | By 21+2 days after completion of antibiotic dosing. | 
| Duration of diarrhea | Number of sequential days with diarrhea. Defined as the time until the first normalization of the stool form according to BSS: presence of one or two sequential normal stools, i.e. soft and formed or hard and formed - types 1-4 per BSS (or lack of stool) for a period of 24 hours. | By 21+2 days after completion of antibiotic dosing. | 
| Antibiotic-associated adverse experiences (abdominal pain, bloating, passing gas, nausea) | Presence of abdominal pain, bloating, passing gass, nausea - Yes/No. | By 21+2 days after completion of antibiotic dosing. | 
| Visual-analogue scale for the gastrointestinal quality of life (VAS-QoL) | Measured via Visual-analogue scale for the gastrointestinal quality of life. The subjects will answer the question: To what extent the abdominal problems impact your quality of life? This scale has numerical points from 0 to 100. 100 indicates THE WORST quality of life one can imagine, 0 indicates NO problems and THE BEST quality of life one can imagine. | By 21+2 days after completion of antibiotic dosing. | 
| Adverse events (AE) | Incidence of mild (for example, self-resolving), moderate (for example, those requiring medical evaluation) and serious AEs (for example, events requiring lasting hospitalization) adverse events. | By 21+2 days after completion of antibiotic dosing. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotics, Antibiotics, Antibiotic-associated diarrhea, High-dose, Multistrain