Intermittent versus daily vitamin D supplementation in children with chronic kidney disease stages 3 to 5 – A Non-Inferiority Trial

This is a single-center, open-label, randomized controlled non-inferiority trial aims to compare the efficacy and safety of monthly versus daily vitamin D supplementation in children aged 1 to 14 years with chronic kidney disease (CKD) stages 3–5. The study will recruit 234 participants with baseline serum vitamin D levels between 12–50 ng/mL and an eGFR < 60 mL/1.73 m²/hr. Participants will be randomized into two groups: one receiving monthly cholecalciferol (60,000 IU) and the other receiving daily cholecalciferol (2,000 IU) for six months. The primary objective is to compare 25-hydroxyvitamin D (25OHD) levels at 3 and 6 months. Secondary objectives include assessing serum calcium, phosphate, intact parathyroid hormone (iPTH), bone turnover markers (bone-specific alkaline phosphatase, TRACP-5b, CTX-I), and bone mineral density (BMD) via DEXA at baseline and 6 months. Routine biochemical tests, including serum electrolytes, creatinine, eGFR, and urine calcium-creatinine ratio, will also be evaluated. Participants will be monitored for compliance, adverse events, and treatment-emergent complications. With sample sizes of 117 in Group A and 117 in Group B, the study is designed to achieve 80% power to detect non-inferiority using a one-sided, two-sample t-test. The margin of non-inferiority is set at -0.100. The assumed true difference between the means is 5.500. The significance level (alpha) of the test is 0.05. The sample size was calculated from study populations with standard deviations of 18.910 and 15.130. Statistical analyses will be conducted using SPSS version 26.0. Descriptive statistics will be utilized to summarize demographic data, medical diagnoses, and clinical characteristics of the patients. Categorical variables will be expressed as frequency (percentage), while continuous variables will be presented as mean ± standard deviation (SD) or median and interquartile range (IQR) as appropriate. Associations between qualitative variables will be assessed using the chi-square test or Fisher’s exact test. The normality of continuous variables will be evaluated using the Shapiro-Wilk test, and accordingly, the Student’s t-test or Mann-Whitney U test will be applied.