A Randomized Controlled Trial of Intravenous versus Oral Cyclophosphamide in Steroid-resistant Nephrotic Syndrome in Children

This is a randomized, parallel group, active-controlled trial to compare the efficacy of intravenous cyclophosphamide (IVCP) with oral cyclophosphamide (OCP) in patients with steroid-resistant nephrotic syndrome (SRNS) in children. Fifty consecutive children with idiopathic SRNS were biopsied and then randomized to receive either OCP at a dose of 2 mg/kg/day for 12 weeks or IVCP at a dose of 500 mg/m²/month for 6 months. Both groups received tapering doses of oral steroids. The response was evaluated in terms of induction of complete remission (CR) or partial remission (PR), time to remit, and side effects. The groups were followed up to determine the duration of remission, percentage of patients who remain in sustained remission for more than 1 year after completion of therapy, change in steroid response status, progression to chronic kidney disease stage 3 or more. Of the fifty patients, OCP was given to 25 children and IVCP to 25 children. The demographic data, histopathology, biochemical profile, and duration of follow-up in the two groups were comparable. The rates of induction of CR were 52% versus 44% and of PR were 8% versus 8% in the intravenous (IV) and oral group, respectively. Time to remit was shorter with OCP than IVCP (53 days vs. 84.4 days). Incidence of side effects (both major and minor) was 36% in IVCP versus 20% in OCP group. The actuarial cumulative sustained remission in our study was 12% in IVCP compared with 16% in OCP at 1 year after completion of therapy. Twelve percent children in both the groups exhibited restoration of steroid sensitivity. Thus, in our study, overall, more than half of SRNS patients showed initial response to cyclophosphamide, but only one-fourth patients had sustained remission on follow-up. OCP and IVCP were equally efficacious and safe in idiopathic SRNS in children.