Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03647995 |
| Other study ID # |
ProbioSJU |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2018 |
| Est. completion date |
February 2, 2019 |
Study information
| Verified date |
October 2020 |
| Source |
Saint-Joseph University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The objective of this study is to determine the efficacy of probiotics containing 25Bn
(billion) CFU (colony-forming unit) of Lactobacillus rhamnosus, Sacchromyces boulardii and
Bifidobacterium breve in the prevention of antibiotic induced diarrhea and Clostridium
difficile diarrhea.
The chosen population consists of 190 hospitalized patients taking antibiotics. Preselected
and randomized patients will take probiotics once daily until 1 week after the course of
antibiotic is over or a placebo with 0 CFU.
The primary outcome is to detect the occurrence of an antibiotic-associated diarrhea. The
secondary outcome is to assess the presence of Clostridium difficile toxins in stool culture.
Description:
Antibiotic-associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) are
a common nosocomial complication following antibiotic use. AAD and CDAD are most importantly
associated with an increase in morbidity and mortality -especially in the elderly population-
thus also contributing to a significant financial burden.
It was reported that 5-25% of patients on antibiotics will develop an AAD of which 10-20% are
caused by Clostridium difficile. Furthermore, the widespread use of broad spectrum
antibiotics is contributing to the increased incidence of CDAD.
The adult human intestinal tract contains up to 100 trillion micro-organisms. This microbiota
is essential and injury to this barrier can result in multiple GI diseases such as infection
by pathogens.
Probiotics are defined as "live micro-organisms which when administered in adequate amounts
confer a health benefit on the host" [WHO 2007]. Many studies suggest that the use of
probiotics and probiotic containing milks will significantly decrease the risk of AAD and
maybe even CDAD.
This study is a randomized double-blind, placebo controlled trial using probiotics containing
25 Bn (billion) CFU of which: 5Bn CFU Lactobacillus rhamnosus, 5Bn CFU Sacchromyces
boulardii, 5Bn CFU Bifidobacterium breve, 4.5Bn CFU Bifidobacterium lactis, 2.5 Bn CFU
Lactobacillus acidophilus, 2.5Bn CFU Lactobacillus plantarum and 500Mn (million) CFU
Lactobacillus reuters or a placebo containing 0 CFU in order to assess the role of probiotics
in the prevention of AAD and CDAD.
Diarrhea is defined as more than two liquid stools for a period greater than 3 days and which
is considered by the patient as an increase in stool quantity compared to regular basis. This
issue will be recorded by the intern/resident. However; if the patient starts his antibiotic
regimen in the hospital and is later discharged at home; the patient will be kept in direct
contact with a specific intern/resident and will inform him of the presence of diarrhea.
The presence of Clostridium Difficile Toxins A and/or B while on antibiotics and for a month
after that will be assessed in the context of diarrhea in hospitalized patients only.
Our patients will be recruited from Hotel-Dieu de France hospital. This includes patients of
all ages who are prescribed antibiotics (single or multiple; oral or IV) assuming that they
are able to eat/drink so that they can take the probiotic pills.
Patients also need to be able to sign a consent form by themselves.
Both groups (probiotic and placebo) will begin treatment within a maximum of 48 hours after
the start of the antibiotic regimen and for the entire duration of antibiotic therapy. This
regimen will be continued a week after the antibiotic therapy is stopped. Researchers will
verify patients' compliance on a daily basis in the hospital and on a weekly basis once the
patient is discharged.
The exclusion criteria are the following: diarrhea on admission; bowel pathology that could
result in diarrhea (eg. IBD), bowel surgeries and pouches; immunocompromised state (including
febrile aplasia, immunosuppressive therapy, ICU patients, HIV-positive patients and renal
transplant patients); prosthetic heart valves or history of endocarditis and rheumatic heart
disease; use of metronidazole, vancomycin or fidaxomycin prior to stool culture for
Clostridium difficile toxins.
Via our computerized medical system, investigators will be able to identify patients who
start an antibiotic regimen. Those who match the trial's inclusion and exclusion criteria
will be included in the trial after a written consent form is obtained.
The hospital pharmacy will provide them with probiotic or placebo boxes each containing 30
capsules that look similar.
Once the antibiotic regimen is finished, the probiotic/placebo course is continued for
another week with a final follow up 4 weeks after the last course of antibiotics. If the
patient is discharged before the end of his antibiotic course, he will be given enough
probiotics/placebo until the end of his antibiotic course and for a week after that. Those
patients will be followed with a weekly phone call and a final follow up 4 weeks after the
last course of antibiotics.
If the patient presents with diarrhea in the hospital, a stool sample will be collected to
check for Clostridium Difficile Toxins A and B.
If these cultures come back positive, the probiotic/placebo regimen is then stopped.
In order to detect an absolute difference of 20% between the proportion of patients in the
placebo group with AAD (considered 30%) and the probiotic group (considered 10%) with α=0.05
and a power of 90% we estimated that we needed a sample size of 164 (82 in each group).
Researchers furthermore considered a 10% risk of loss of contact with the patient and
therefore estimated a sample size of 180 (90 in each group).
