SUMMARY OF PROTOCOL

Research question: Does zinc play a role on the course of acute diarrhea in adult patients?

Study title: Role of zinc in adults with acute diarrhea: A randomized controlled trial

Rationale: Use of zinc in children with acute diarrhea is well established with WHO recommending zinc supplementation as an adjunct to the standard ORS. Research about the use of zinc in adult diarrhea is scarce. As zinc is a cost-effective supplement with a well-established use in children, this study is being done if zinc supplementation during the course of diarrhea will benefit the adult patient as much as it does in children.

Aim: To study the role of zinc supplementation in adults suffering from acute diarrhea

Objectives

Primary objective:

To find out the difference in the proportion of the patients with resolution of diarrhea by day 5.

Secondary objective:

To find out the proportion of patients developing complications of acute diarrhea in the treatment and the control groups.

Setting: The study will be conducted on patients visiting Medicine Emergency and Medicine wards University College of Medical Sciences and GTB Hospital, Delhi.

Study design: Open-label Randomized Controlled Trial

Time Frame: May 2023 to October 2024

Participants: Adult patients (≥ 18 years) coming to Medicine emergency and getting admitted in medicine wards with Acute diarrhea (diarrhea lasting for upto 14 days).

Inclusion criteria for cases

·       Any patient aged  ≥18 years presenting with acute diarrhea (diarrhea lasting for  â‰¤ 14 days)

Exclusion Criteria for cases

·       Known cases of Inflammatory bowel disease, irritable bowel syndrome, celiac disease or any other known causes of malabsorption syndromes.

·       Patients who are on immunosuppressant therapy, cancer chemotherapy and radiotherapy

·       Known cases of HIV.

·       Any patients on laxatives.

·       Patients with history of bowel resection or other major bowel surgeries

METHODS

All patients who give consent for the study and who satisfy the inclusion and exclusion criteria will be considered for the study. Randomization and allotment concealment will be done. Sequentially numbered opaque sealed envelopes will contain the code of medication to be given to the participant. All the patients will receive standard care including ORS, iv fluids and antibiotics and the patient in the test group will receive tab zinc sulphate with 50 mg elemental zinc in addition. All the drugs used will be from the hospital pharmacy.

Detailed clinical history, examination and investigations will be carried out as per the case record sheet (chief complaints, history of presenting complaints, general physical examination, systemic examination and routine investigations). Serial blood investigations will be done in patients developing complications to monitor their progression and resolution. Investigations like stool and urine examinations will be conducted according to the suspected etiology..

OUTCOME MEASURES:

Primary outcome measures:

The difference in the proportion of the patients with resolution of diarrhea by day 5 in the intervention group compared to the control group.

Secondary outcome measures:

The proportion of patients developing complications in the intervention group compared to the control group.

Sample size:

Sample size calculation was done using the formula for sample size calculation for comparing proportions(1)

n = (Zα/2 + Zβ)² * (p1(1 - p1) + p2 (1 - p2)) / (p1 - p2)²

In order to estimate a 10% difference between the group of patients receiving zinc supplementation and the placebo group suffering from diarrhea and expecting that 100% of patients receiving Zinc supplement recover by day 5, with type 1 error of 5% and power of 80, the sample size was calculated to be 77 in each group totaling to 154 for the study.

Statistical analysis:

·       The difference in the proportion of recovery rate between the two groups will be compared by Chi-square test.

·       Intention to treat principle will be applied for the comparison of the outcome between the two groups

·       In case of missing values due to loss to follow up and we were not able to get the information about the outcome in spite of our best effort, we will impute the missing outcome value by randomly selecting one of two possible outcomes defined in the study.