Comparison of the efficacy of steroid tapering over 4-weeks with 8-weeks in children with frequently relapsing or steroid dependent nephrotic syndrome on a steroid-sparing agent presenting with a relapse - A non-inferiority randomised controlled trial

The study shall be undertaken at the Dept of Paediatrics, JIPMER from July 2024 for a period of 2 years after acquiring the Institutional Ethics Committee (IEC) clearance and CTRI registration prior to enrolment of the first patient. This study shall include patients aged 1 to 18 years with frequently relapsing or steroid dependent nephrotic syndrome who are on a steroid sparing agent for the preceding 2 months. When these patients present with a relapse, they will be approached for possible enrolment into the trial. Written informed consent will be taken from the parents of the study participants (and assent from children 8 years or older) and the study will be conducted in accordance with the Declaration of Helsinki.

Once patients are enrolled, the weight of the child will be recorded with an electronic weighing machine with a precision of 10 g. The height will be recorded with the help of a manual stadiometer with a precision of 0.1 cm. The dose of prednisolone calculated according to the body weight will be rounded off to the nearest multiple of 2.5. Prednisolone will be administered in the form of tablets (minimal strength 5 mg), which can be broken into half, if required.

They will receive standard treatment for relapse i.e. daily prednisolone at 2 mg/kg (maximum 60 mg) till remission followed by 1.5 mg/kg (maximum 40 mg) alternate day prednisolone for 4 weeks. Subsequently, they will be randomised to one of the two arms (intervention vs control group) and the steroid treatment in each of these arms will be as per the mentioned protocol. The cumulative steroid dose will be calculated in mg/kg. All patients will also receive the steroid-sparing agent they were already on, apart from calcium supplements. The dose of the steroid-sparing agents will be as per the prevailing standard of care in the unit, which is in line with the ISPN 2022 guidelines.

Subsequently, all enrolled patients will be followed up monthly for the next 6 months for the primary outcome and 12 months for the secondary outcome. During each follow-up visit, medications will be checked (pill count) and further medications for the next 30 days will be given. The urine protein diary monitored by the patients at home will be checked and the details entered in a predesigned proforma. Patients will undergo spot urinary protein dipstick and urine spot protein-creatinine ratio in each monthly visit and blood tests for CBC, albumin, creatinine, cholesterol once in 3 months; hsCRP will be checked at enrollment and at 6 months. Eye check up for cataract and glaucoma will be checked at baseline and at 6 months.