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

NCT05607056 | Completed

• 2 other identifiers: SPAADA202211_0012022-002817-40
• Study Type: interventional
• Target: 565
• Locations: 1 country
• Sites: 3

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.

Conditions

Antibiotic-associated Diarrhea

Keywords

Probiotics; Antibiotics; Antibiotic-associated diarrhea; High-dose; Multistrain

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Severity of AAD

  By 21+2 days after completion of antibiotic dosing.

• Duration of diarrhea

  By 21+2 days after completion of antibiotic dosing.

• Antibiotic-associated adverse experiences (abdominal pain, bloating, passing gas, nausea)

  By 21+2 days after completion of antibiotic dosing.

• Visual-analogue scale for the gastrointestinal quality of life (VAS-QoL)

  By 21+2 days after completion of antibiotic dosing.

• Adverse events (AE)

  By 21+2 days after completion of antibiotic dosing.

Study Arms (2)

Probiotic

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Sinquanon DIETARY_SUPPLEMENT

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.

Probiotic

Placebo DIETARY_SUPPLEMENT

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neopharm Bulgaria Ltd.: lead

Study Sites (3)

University Hospital "St George"

Plovdiv, 4002, Bulgaria

Location

University Hospital for Pulmonary Diseases " St. Sofia"

Sofia, 1431, Bulgaria

Location

University Hospital "Tsaritsa Yoanna - ISUL"

Sofia, 1527, Bulgaria

Location

Related Publications (11)

• 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.

  PMID: 33207631 BACKGROUND

• 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.

  PMID: 26793178 BACKGROUND

• 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.

  PMID: 32087535 BACKGROUND

• 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.

  PMID: 12052785 BACKGROUND

• 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.

  PMID: 26365389 BACKGROUND

• 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.

  PMID: 26216624 BACKGROUND

• 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.

  PMID: 28008787 BACKGROUND

• 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.

  PMID: 26756877 BACKGROUND

• 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.

  PMID: 26695080 BACKGROUND

• 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.

  PMID: 20145608 BACKGROUND

• Hodzhev V, Dzhambazov K, Sapundziev N, Encheva M, Todorov S, Youroukova V, Benchev R, Nikolov R, Bogov B, Momekov G, Hadjiev V. High-dose Probiotic Mix of Lactobacillus spp., Bifidobacterium spp., Bacillus coagulans, and Saccharomyces boulardii to Prevent Antibiotic-associated Diarrhea in Adults: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial (SPAADA). Open Forum Infect Dis. 2024 Oct 21;11(11):ofae615. doi: 10.1093/ofid/ofae615. eCollection 2024 Nov.

  PMID: 39529939 DERIVED

Study Officials

• 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, Bulgaria

  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

  PRINCIPAL INVESTIGATOR

• Vladimir Hodzhev, Prof, PhD

  University Hospital "St George"

  PRINCIPAL INVESTIGATOR

• Spiridon Todorov, Prof, PhD

  University Hospital "Tsaritsa Yoanna - ISUL"

  PRINCIPAL INVESTIGATOR

• Vania Youroukova, Prof, PhD

  University Hospital for Pulmonary Diseases " St. Sofia"

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, multicenter, double-blind, placebo-controlled, randomized, parallel-arm clinical study

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 7, 2022
• Study Start: November 27, 2022
• Primary Completion: March 20, 2023
• Study Completion: April 25, 2023
• Last Updated: October 21, 2024

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

BU (3)