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

Primary Purpose

Antibiotic-associated Diarrhea

Status
Completed
Phase
Not Applicable
Locations
Bulgaria
Study Type
Interventional
Intervention
Sinquanon
Placebo
Sponsored by
Neopharm Bulgaria Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Antibiotic-associated Diarrhea focused on measuring Probiotics, Antibiotics, Antibiotic-associated diarrhea, High-dose, Multistrain

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Hospital "St George"
  • University Hospital for Pulmonary Diseases " St. Sofia"
  • University Hospital "Tsaritsa Yoanna - ISUL"

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Probiotic

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Antibiotic-associated adverse experiences (abdominal pain, bloating, passing gas, nausea)
Presence of abdominal pain, bloating, passing gass, nausea - Yes/No.
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.
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.

Full Information

First Posted
October 31, 2022
Last Updated
July 25, 2023
Sponsor
Neopharm Bulgaria Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05607056
Brief Title
Efficacy and Safety of Sinquanon for Prevention of Antibiotic-associated Diarrhea in Adults
Acronym
SPAADA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
November 27, 2022 (Actual)
Primary Completion Date
April 20, 2023 (Actual)
Study Completion Date
July 25, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neopharm Bulgaria Ltd.

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
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Antibiotic-associated Diarrhea
Keywords
Probiotics, Antibiotics, Antibiotic-associated diarrhea, High-dose, Multistrain

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective, multicenter, double-blind, placebo-controlled, randomized, parallel-arm clinical study
Masking
ParticipantInvestigator
Masking Description
Investigators will be provided with coded and identical products. Each individual involved in the study will be blinded to the assignment until study completion. Considering the established safety profile of the probiotic strains no necessity is foreseen for urgent unblinding of treatment assignment. With this in mind, no copies of the treatment assignments will be stored at the enrollment sites. If needed, the Investigators may receive information about the assignment of a particular subject only after review and approval by the Medical monitor. No information about the subjects will be shared with the company conducting the randomization.
Allocation
Randomized
Enrollment
565 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Probiotic
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Sinquanon
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Antibiotic-Associated diarrhea (AAD)
Description
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.
Time Frame
By 21+2 days after completion of antibiotic dosing.
Secondary Outcome Measure Information:
Title
Severity of AAD
Description
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.
Time Frame
By 21+2 days after completion of antibiotic dosing.
Title
Duration of diarrhea
Description
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.
Time Frame
By 21+2 days after completion of antibiotic dosing.
Title
Antibiotic-associated adverse experiences (abdominal pain, bloating, passing gas, nausea)
Description
Presence of abdominal pain, bloating, passing gass, nausea - Yes/No.
Time Frame
By 21+2 days after completion of antibiotic dosing.
Title
Visual-analogue scale for the gastrointestinal quality of life (VAS-QoL)
Description
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.
Time Frame
By 21+2 days after completion of antibiotic dosing.
Title
Adverse events (AE)
Description
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.
Time Frame
By 21+2 days after completion of antibiotic dosing.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Georgi Momekov, Prof PhD
Organizational Affiliation
Department of Pharmacology, Pharmacotherapy and Toxicology, Medical University of Sofia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Karen Dzhambazov, Prof, PhD
Organizational Affiliation
University hospital for active treatment Sveti Georgi, Medical University-Plovdiv
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nikolay Sapundziev, Prof, PhD
Organizational Affiliation
Department of Neurosurgery and Otorhinolaryngology, Medical University - Varna
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Milena Encheva, MD, PhD
Organizational Affiliation
Military Medical Academy
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Boris Bogov, Prof, PhD
Organizational Affiliation
UMHAT "Sveta Anna"
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rosen Nikolov, Prof, MD
Organizational Affiliation
UMHAT St Ivan Rilski
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rumen Benchev, Prof
Organizational Affiliation
Hill Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vladimir Hodzhev, Prof, PhD
Organizational Affiliation
University Hospital "St George"
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Spiridon Todorov, Prof, PhD
Organizational Affiliation
University Hospital "Tsaritsa Yoanna - ISUL"
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vania Youroukova, Prof, PhD
Organizational Affiliation
University Hospital for Pulmonary Diseases " St. Sofia"
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital "St George"
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
University Hospital for Pulmonary Diseases " St. Sofia"
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
University Hospital "Tsaritsa Yoanna - ISUL"
City
Sofia
ZIP/Postal Code
1527
Country
Bulgaria

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33207631
Citation
Konstantinidis T, Tsigalou C, Karvelas A, Stavropoulou E, Voidarou C, Bezirtzoglou E. Effects of Antibiotics upon the Gut Microbiome: A Review of the Literature. Biomedicines. 2020 Nov 16;8(11):502. doi: 10.3390/biomedicines8110502.
Results Reference
background
PubMed Identifier
26793178
Citation
Francino MP. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Front Microbiol. 2016 Jan 12;6:1543. doi: 10.3389/fmicb.2015.01543. eCollection 2015.
Results Reference
background
PubMed Identifier
32087535
Citation
Mekonnen SA, Merenstein D, Fraser CM, Marco ML. Molecular mechanisms of probiotic prevention of antibiotic-associated diarrhea. Curr Opin Biotechnol. 2020 Feb;61:226-234. doi: 10.1016/j.copbio.2020.01.005. Epub 2020 Feb 19.
Results Reference
background
PubMed Identifier
12052785
Citation
Barbut F, Meynard JL. Managing antibiotic associated diarrhoea. BMJ. 2002 Jun 8;324(7350):1345-6. doi: 10.1136/bmj.324.7350.1345. No abstract available.
Results Reference
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PubMed Identifier
26365389
Citation
Szajewska H, Kolodziej M. Systematic review with meta-analysis: Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea in children and adults. Aliment Pharmacol Ther. 2015 Nov;42(10):1149-57. doi: 10.1111/apt.13404. Epub 2015 Sep 13.
Results Reference
background
PubMed Identifier
26216624
Citation
Szajewska H, Kolodziej M. Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2015 Oct;42(7):793-801. doi: 10.1111/apt.13344. Epub 2015 Jul 27.
Results Reference
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PubMed Identifier
28008787
Citation
Ouwehand AC. A review of dose-responses of probiotics in human studies. Benef Microbes. 2017 Apr 26;8(2):143-151. doi: 10.3920/BM2016.0140. Epub 2016 Dec 23.
Results Reference
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PubMed Identifier
26756877
Citation
Szajewska H, Canani RB, Guarino A, Hojsak I, Indrio F, Kolacek S, Orel R, Shamir R, Vandenplas Y, van Goudoever JB, Weizman Z; ESPGHAN Working Group for ProbioticsPrebiotics. Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Children. J Pediatr Gastroenterol Nutr. 2016 Mar;62(3):495-506. doi: 10.1097/MPG.0000000000001081.
Results Reference
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PubMed Identifier
26695080
Citation
Goldenberg JZ, Lytvyn L, Steurich J, Parkin P, Mahant S, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2015 Dec 22;(12):CD004827. doi: 10.1002/14651858.CD004827.pub4.
Results Reference
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PubMed Identifier
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Citation
Gao XW, Mubasher M, Fang CY, Reifer C, Miller LE. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol. 2010 Jul;105(7):1636-41. doi: 10.1038/ajg.2010.11. Epub 2010 Feb 9.
Results Reference
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Efficacy and Safety of Sinquanon for Prevention of Antibiotic-associated Diarrhea in Adults

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