Prevention of Antibiotic-Associated Diarrhoea With Prolardii
Prevention of Antibiotic-Associated Diarrhoea With Prolardii
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.
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.
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.