Double-Blind Randomized Study to Evaluate the Effect of Hydroxycarbamide on Albuminuria in Adults with Sickle Cell Disease: Sikamic (SIklos on Kidney Function and AlbuMInuria Clinical Trial)

Background Sickle cell disease (SCD) is associated with a high frequency of chronic kidney disease, which is an independent risk factor for mortality in this population. SCD-associated nephropathy (SCAN) is an emerging concern, characterized by significant albuminuria and progressive deterioration of renal function with a prevalence of up to 26% to 68% in SCD adult patients (Falk 1992, Powars 2005, Yeruva 2016, Ataga 202). Because of rapid decline of estimated glomerular filtration rate (eGFR) is a frequent finding in this population (Derebail 2019, Ataga KI 2021), early diagnosis of SCAN and identification of associated clinical and biologic risk factors are crucial for initiating kidney-protective therapy at early stages of renal impairment. Albuminuria serves as a relevant biomarker for detecting early glomerular damage in SCD patients (Audard 2017). To date, Hydroxycarbamide (HU) remains the cornerstone treatment for managing SCD patients, and its efficacy is primarily attributed to its ability to increase fetal hemoglobin (HbF) levels (Segal 2008). Several observational studies conducted in adult SCD patients have shown that HU may have renal protective effects, making it a promising therapeutic option, but until now, randomized clinical trials confirming this hypothesis are missing (Bartolucci 2015, Laurin 2014). Method SIKAMIC (SIklos on Kidney Function and AlbuMInuria Clinical Trial) is an international (France and Africa), phase IIb, double-blind, randomized, placebo-controlled study. The main objective is to assess the effect of HU on albuminuria levels in SCD adult patients after 6 months of treatment. Eligible patients are of the SS or Sβ0 genotype with a mean albuminuria value (assessed by albumin-to-creatinine ratio: ACR) above 3 and less than 100 mg/mmol, on three urine samples taken one day apart. Patients should not have received HU treatment within the previous 6 months and should not be taking conventional kidney-protecting measures (ACE inhibitors or ARA2) and having blood transfusion in the last 3 months. Patient with an eGFR rate < 60 and ≥ 140 ml/min/1,73m² are excluded from the study. Patients receive either HU at a dosage of 15mg/kg/day or placebo for 6 months, and responders (patient achieving at least a 30% decrease of the ACR baseline at 6 months) have the option to continue the study for an additional six months. Recruitment started in August 2019 in France and in October 2021 in Africa and was extended until June 2023 due to c