Comparison of Two Probiotics for Reducing Diarrhea Frequency in Children Aged 6-24 Months

- Background and Rationale

Acute watery diarrhea is an important cause of morbidity among children under five years of age, particularly in resource-limited settings. In young children, ongoing fluid loss can result in dehydration and may lead to serious complications if appropriate management is delayed. The mainstay of treatment is oral rehydration therapy (ORS), zinc supplementation, continued breastfeeding, and appropriate dietary management. Probiotics have also been used as adjuncts to standard treatment, with the aim of improving clinical recovery. However, the effectiveness of probiotics may vary according to the specific microorganism and strain used.

Saccharomyces boulardii CNCM I-745 is a yeast probiotic that has been investigated for its role in pediatric acute gastroenteritis. Bacillus clausii is a spore-forming bacterial probiotic, and the four strains O/C, SIN, N/R, and T have also been used in the management of gastrointestinal disorders, including diarrhea in children. Although both preparations have been studied individually, direct comparisons between these probiotic preparations in children with acute watery diarrhea remain limited.

Differences in their biological characteristics and the limited availability of direct comparative evidence provide a rationale for evaluating these two preparations within the same clinical setting and study population. Such a comparison may contribute to a better understanding of their relative effectiveness when used alongside standard treatment.

- Study Purpose

The purpose of this study is to compare the effectiveness of *Saccharomyces boulardii* CNCM I-745 and a four-strain preparation of *Bacillus clausii* (O/C, SIN, N/R, and T) in reducing the daily frequency of acute watery diarrhea in young children.

The study focuses on the change in the frequency of diarrhea episodes during the treatment and observation period. The comparison is intended to determine whether the two probiotic preparations differ in their effectiveness when administered with standard management for acute watery diarrhea.

- Study Design and Conduct

This is a randomized, open-label clinical trial conducted in the Children Emergency and Outpatient Department of Paediatric Medicine Unit-II, King Edward Medical University / Mayo Hospital, Lahore, Pakistan.

The study plans to include 88 children, with 44 participants allocated to each treatment group. Participants will be selected using non-probability convenient sampling from children presenting to the study setting who meet the protocol-defined selection criteria. After assessment for eligibility and obtaining written informed consent from a parent or guardian, participants will be allocated to one of the two groups using a lottery method.

The study is open-label, meaning that treatment allocation is not blinded to the participants' caregivers or the study team. Both groups will receive the same general standard management for diarrhea, including oral rehydration therapy, zinc supplementation, and dietary advice. This approach allows the daily frequency of diarrhea to be compared between the two probiotic treatment groups under the same clinical setting and observation period.

- Clinical Assessment and Data Collection

At enrollment, a clinical assessment will be performed, and relevant demographic and clinical information will be recorded on the study proforma. This includes age, sex, weight, vital signs, the onset of diarrhea, and the reported frequency of diarrhea during the preceding 24 hours. Clinical assessment will also establish whether the child meets the protocol's definition of acute watery diarrhea with some dehydration.

During the study period, the frequency of diarrhea episodes will be documented daily. Participants will be followed for three days after admission, and the recorded information will be used to compare the two groups. The study will assess the daily stool frequency observed during follow-up rather than assume that one probiotic is more effective than the other.

- Data Analysis and Interpretation

Study data will be entered and analyzed using Statistical Package for the Social Sciences (SPSS), version 26. Quantitative variables, including age, weight, and stool frequency, will be summarized using means and standard deviations. The independent-samples t-test will be used for comparisons of quantitative variables as specified in the study protocol. Qualitative variables, including sex, dehydration status, and nutritional status, will be summarized as frequencies and percentages and compared using the chi-square test. A p-value of less than 0.05 will be considered statistically significant.

The findings will be interpreted by comparing the recorded diarrhea frequency between the two treatment groups. The results may help inform clinical decision-making regarding the choice of probiotic as an adjunct to standard treatment in children with acute watery diarrhea. The study is intended to provide evidence from a local pediatric clinical setting; its findings will be interpreted in the context of its sample size, study design, and follow-up period.