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

Sponsor

Neopharm Bulgaria Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05607056

Collaborator

(none)

630

Enrollment

Locations

Arms

Anticipated Duration (Months)

210

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Antibiotic-associated Diarrhea	Dietary Supplement: Sinquanon Dietary Supplement: Placebo	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

630 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, multicenter, double-blind, placebo-controlled, randomized, parallel-arm clinical studyProspective, multicenter, double-blind, placebo-controlled, randomized, parallel-arm clinical study

Masking:

Double (Participant, Investigator)

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.

Primary Purpose:

Prevention

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

Actual Study Start Date :

Nov 27, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Probiotic 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 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.
Placebo Comparator: Placebo 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 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.

Arm

Intervention/Treatment

Experimental: Probiotic

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

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.

Placebo Comparator: Placebo

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

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.

Outcome Measures

Primary Outcome Measures

Incidence of Antibiotic-Associated diarrhea (AAD) [By 21+2 days after completion of antibiotic dosing.]
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 [By 21+2 days after completion of antibiotic dosing.]
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 [By 21+2 days after completion of antibiotic dosing.]
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) [By 21+2 days after completion of antibiotic dosing.]
Presence of abdominal pain, bloating, passing gass, nausea - Yes/No.
Visual-analogue scale for the gastrointestinal quality of life (VAS-QoL) [By 21+2 days after completion of antibiotic dosing.]
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) [By 21+2 days after completion of antibiotic dosing.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Hospital "St George"	Plovdiv	Bulgaria	4002
2	University Hospital for Pulmonary Diseases " St. Sofia"	Sofia	Bulgaria	1431
3	University Hospital "Tsaritsa Yoanna - ISUL"	Sofia	Bulgaria	1527

Sponsors and Collaborators

Neopharm Bulgaria Ltd.

Investigators

Principal Investigator: Georgi Momekov, Prof PhD, Department of Pharmacology, Pharmacotherapy and Toxicology, Medical University of Sofia
Principal Investigator: Karen Dzhambazov, Prof, PhD, University hospital for active treatment Sveti Georgi, Medical University-Plovdiv
Principal Investigator: Nikolay Sapundziev, Prof, PhD, Department of Neurosurgery and Otorhinolaryngology, Medical University - Varna
Principal Investigator: Milena Encheva, MD, PhD, Military Medical Academy
Principal Investigator: Boris Bogov, Prof, PhD, UMHAT "Sveta Anna"
Principal Investigator: Rosen Nikolov, Prof, MD, UMHAT St Ivan Rilski
Principal Investigator: Rumen Benchev, Prof, Hill Clinic