Alfacalcidol 1micrograms/5ml oral suspension

IntroductionMinimal change disease (MCD) is a frequent cause of nephrotic syndrome in adults. Standard treatment consists of high-dose prednisolone (1 mg/kg/d), which induces remission in over 80% of patients but is associated with considerable glucocorticoid toxicity. Here, in the ADAPT trial, we investigated whether a lower dose of prednisolone combined with activated vitamin D (alfacalcidol) could be non-inferior to the standard high-dose regimen in achieving remission.MethodsIn this randomized, open-label, non-inferiority, multicenter trial, 67 adults with MCD were assigned to either lower-dose prednisolone with alfacalcidol or standard high-dose prednisolone. The primary endpoint was remission rate. Secondary endpoints included time to remission, relapse rate, time to relapse, incidence of serious adverse events and glucocorticoid-related toxicity.ResultsAlthough statistical non-inferiority was not established, rates, time to remission and relapse were comparable between groups. Remission was achieved in 88% (95% confidence interval: 74-96) of patients in the lower-dose prednisolone/alfacalcidol group and in 91% (78-98) of those receiving high-dose prednisolone. Median time to remission was 28 days [interquartile range 14-54] versus 23 days [13-47], respectively. Relapses occurred in 35% and 32% of patients, with median times to relapse of 195 days [100-275] and 179 days [161-206], respectively. The total cumulative doses of prednisolone were significantly less 3.7 g vs 8.0 g, respectively. The number of serious adverse events were less and glucocorticoid-related toxicities (46 [11-77] vs. 74 [30-119]) were significantly less in the lower-dose/ alfacalcidol group than the high-dose group, respectively.ConclusionsNon-inferiority was not reached for the combined intervention with lower dose prednisolone and alfacalcidol compared to standard prednisolone treatment. But the combined treatment offers a safer alternative to high-dose prednisolone for treatment of MCD, with similar efficacy but fewer serious adverse events and reduced glucocorticoid toxicity.Trial registrationRegistered at ClinicalTrials.gov with study number NCT03210688.

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