In this study, the randomized block design with 4-tuple randomization method is used for random allocation. In this method, different permutations of the two treatment groups (A and B) are randomly arranged in each 4-tuple block. The possible permutations include ABAB, BABA, AABB, BBAA, ABBA, and BAAB. To generate these blocks, the website www.sealedenvelope.com is used, which provides a tool for generating random assignments and random block allocations in clinical studies. This website uses randomization algorithms to generate the required sequence completely randomly and without human intervention. Then, using a random number table and assigning numbers from 0 to 9 to each permutation, a random list consisting of 15 blocks of 4-tuple (which totals 60 samples) is created. This random sequence is used to allocate treatment and control groups to the participants, ensuring that the distribution of groups is balanced at each stage.
In this study, all participants, their companions, investigators, and healthcare staff responsible for patient care will remain unaware of the group allocations until the study is completed. This means that the investigator and the individual conducting the sampling, like the participants themselves, will not know which patient is receiving the zinc supplement or the placebo. Both patients and their companions will also be unaware of the type of pill being given. The drugs and placebos will be coded by someone who is completely blinded to the study process, and the code will be placed in an envelope that indicates whether it's the drug or the placebo. One group will receive drug A, and the other group will receive drug B. Furthermore, the zinc supplement and placebo tablets, which are identical in color, size, and shape, will be used in the study. Therefore, this will be a double-blind study. The placebo tablets will contain starch and will look, smell, and feel identical to the zinc supplement tablets.