Clinical trial NCT03256708: Prevention of Antibiotic-Associated Diarrhoea With Prolardii
Official title: Double-blind Randomised Placebo-controlled Study of Prolardii Gastro-resistant (GR) Caps in the Prevention and Treatment of Antibiotic-associated Diarrhoea.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Antibiotic-associated Diarrhea
Keywords: antibiotic-associated diarrhea
probiotic
prebiotic
placebo
synbiotic
Lead sponsor: Therabel Pharma SA/NV
Sponsor class: INDUSTRY
Collaborators: name: ECSOR
First posted: 2017-08-22
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind parallel placebo-controlled randomized study
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Prevention of antibiotic-associated diarrhea
timeFrame: Antibiotic treatment duration (7 to 10 days) + 5 days
Secondary outcomes:
measure: Duration of diarrhea
timeFrame: Antibiotic treatment duration (7 to 10 days) + 5 days
measure: Number of bowel movements
timeFrame: Antibiotic treatment duration (7 to 10 days) + 5 days
measure: Tolerability of the study treatment
timeFrame: Antibiotic treatment duration (7 to 10 days) + 5 days
measure: Quality of life of the patients
timeFrame: Antibiotic treatment duration (7 to 10 days) + 5 days
measure: Safety of the study treatment
timeFrame: Antibiotic treatment duration (7 to 10 days) + 5 days
Other outcomes:
Locations:
city: Linkebeek
country: Belgium
facility: ResearchLink
Study officials:
affiliation: Marketing Manager
name: Nicolas Foucart
role: STUDY_DIRECTOR
References: