Prevention of Antibiotic-Associated Diarrhoea With Prolardii (PAADI)

Double-blind Randomised Placebo-controlled Study of Prolardii Gastro-resistant (GR) Caps in the Prevention and Treatment of Antibiotic-associated Diarrhoea.

Prolardii contains intestinal bacteria, a yeast, a fructo-oligosaccharide and a plant extract that can contribute to the intestinal comfort. This product could prevent the diarrhea which sometimes occurs when the patient has to take antibiotics.

A total of 220 patients being prescribed antibiotics by general practitioners will be included in the study and randomized into a Prolardii arm and a placebo arm.

The primary endpoint will be the overall frequency of diarrhea in the two treatment groups. Acute diarrhea will be defined as the presence of three or more abnormally loose or watery stools per day.

Study Overview

• Status: Unknown
• Conditions: Antibiotic-associated Diarrhea
• Intervention / Treatment: Dietary supplement: Prolardii; Dietary supplement: Placebo

Detailed Description

Prolardii is a synbiotic (prebiotic and probiotic) formulation including 4 strains of living lyophilized lactic bacteria (Lactobacillus rhamnosus GG, Bifidobacterium lactis B94, Lactobacillus casei 5773 and Lactobacillus acidophilus LA3), a yeast (Saccharomyces boulardii), a fructo-oligosaccharide (Actilight) and a dry extract of Inula helenium, a plant that can contribute to the intestinal comfort.

Taking into account the international literature, we made the assumption that the combination of probiotics and prebiotics into the same synbiotic product could improve the prevention of antibiotic-associated diarrhea and could also attenuate the intestinal symptoms related to the use of antibiotics. According to our knowledge this association has never been tested in a double-blind, randomised, placebo-controlled study.

The study will be double-blind, parallel-group, randomized, multicentre and placebo-controlled. A total of 220 patients being prescribed broad-spectrum antibiotics by general practitioners will be included in the study and randomized (1:1) into a Prolardii arm (2 capsules per day for 12 to 15 days) and a placebo arm (2 capsules per day for 12 to 15 days). There will be two medical visits (baseline visit and end-of-treatment visit) and one follow-up phone call (4 weeks after the end of treatment). During the treatment, the patients will filled in a diary card on a daily basis. They will record the number of bowel movements, the quality of the stools, the solicited symptoms (flatulence, bloating, abdominal pain/cramps, nausea and vomiting), their quality of life and the use of concomitant medications.

The data will be collected in an electronic case report form. The sample size calculation was based on the following assumptions: an attack rate in the placebo group situated in a range between 20% and 25%, an efficacy of Prolardii of about 60%, a randomization ratio 1:1 between the placebo and the active treatment group, a power of 80% and a Type I error value of 5%. Taking into account these assumptions a total of at least 30 diarrhoea cases should be reached all together in the two treatment groups, in order to ensure a sufficient power.

The primary endpoint will be the overall frequency of diarrhea in the two treatment groups. Acute diarrhea will be defined as the presence of three or more abnormally loose or watery stools per day.

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Linkebeek, Belgium
    • ResearchLink

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• Male or female patient
• Patient aged 18 to 65 years-old
• Patient being prescribed broad spectrum antibiotics for a minimum period of 7 days and a maximum period of 10 days. Broad spectrum antibiotics are aminopenicillins (amoxicillin with or without clavulanic acid, ampicillin), cephalosporins (cefadroxil, cephalexin, cefazolin, cefuroxime, cefotaxime, ceftazidime, ceftriaxone and ceftaroline), fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin), tetracyclines (doxycycline, minocycline), nitrofurans (nitrofurantoin) and/or antibacterial sulfonamides (co-trimoxazol).
• Patient who the investigator believes that they can and will comply with the requirements of the protocol.

Exclusion Criteria:

• Patient treated with antibiotics within 3 months before inclusion in the study
• Pregnant or lactating woman
• Woman wishing to be pregnant
• Immunosuppressed subject
• Subject having a central venous catheter
• History of chronic diarrhoea
• History of irritable bowel syndrome
• History of Crohn's disease
• History of ulcerative colitis
• History of chronic constipation and/or chronic use of laxatives
• Patient with a clinically-active malignancy.
• Patient who participated in a clinical study in the previous three months
• History of psychological disorder, mental dysfunction, alcohol or drug abuse or any other factor which might interfere with the ability to cooperate in the study.
• Patient who is not sufficiently motivated to engage on a follow-up period of approximately 1.5 month, unable to complete the patient diary, or likely to travel or to move before the end of the study
• Intolerance to lactose
• Difficulty or inability to swallow '00' size capsules
• Allergy to one or several ingredients of Prolardii® GR Caps and in particular to yeasts.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolardii; Prolardii GR Caps includes 4 strains of living lyophilized lactic bacteria (Lactobacillus rhamnosus GG, Bifidobacterium lactis B94, Lactobacillus casei 5773 and Lactobacillus acidophilus LA3), a yeast (Saccharomyces boulardii), a fructo-oligosaccharide (Actilight) and a dry extract of Inula helenium.	Dietary supplement: Prolardii; Prolardii: 2 capsules per day for 12 to 15 days
Placebo Comparator: Placebo; Inactive ingredients	Dietary supplement: Placebo; Inactive ingredients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of antibiotic-associated diarrhea	Percentage of patients presenting an acute antibiotic-associated diarrhea	Antibiotic treatment duration (7 to 10 days) + 5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of diarrhea	Number of days of diarrhea	Antibiotic treatment duration (7 to 10 days) + 5 days
Number of bowel movements	Number of defecations	Antibiotic treatment duration (7 to 10 days) + 5 days
Tolerability of the study treatment	Percentage of patients showing solicited symptoms (flatulence, bloating, abdominal pain/cramps, nausea and/or vomiting)	Antibiotic treatment duration (7 to 10 days) + 5 days
Quality of life of the patients	Quality of life score	Antibiotic treatment duration (7 to 10 days) + 5 days
Safety of the study treatment	Percentage of patients with adverse events	Antibiotic treatment duration (7 to 10 days) + 5 days

Collaborators and Investigators

• Sponsor: Therabel Pharma SA/NV
• Collaborators: ECSOR
• Investigators: Study Director: Nicolas Foucart, Marketing Manager

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2017
• Primary Completion (Anticipated): September 1, 2018
• Study Completion (Anticipated): September 1, 2018

Study Registration Dates

• First Submitted: August 18, 2017
• First Submitted That Met QC Criteria: August 18, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): April 3, 2018
• Last Update Submitted That Met QC Criteria: April 1, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: prebiotic; probiotic; synbiotic; placebo; antibiotic-associated diarrhea
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: THE-2017-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No