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Abstract 819 Background. HbSC is characterized by increased red cell density and clinical complications but has rarely been the target of therapeutic trials. The CHAMPS Trial was a prospective, randomized, double-blinded, multi-center Phase II study of HU and Mg in children and adults with HbSC conducted by the Comprehensive Sickle Cell Centers Clinical Trials Consortium. HU is clinically efficacious in HbSS, but its value has not been demonstrated for HbSC; Mg reduces cation transport activity and improves hydration of HbSS erythrocytes. The primary objective of the trial was to measure the ability of HU and Mg individually and in combination to reduce the density of HbSC erythrocytes. Secondary objectives were to determine the effects of the 2 agents on hematologic parameters and red cell pathobiology, to identify toxicities of HU and Mg, and to record adverse events. Methods. Eligible subjects had HbSC and at least 1 vaso-occlusive event in the previous 12 months (but none in the 4 weeks before study entry) and were ≥ age 5 years. After providing informed consent and baseline evaluations, subjects were randomized to 1 of 4 arms: (A) HU (20 mg/kg/d PO) and Mg (0.6 mEq/kg/d PO in 2 doses), (B) HU and placebo for Mg, (C) HU placebo and Mg, or (D) placebos for both. Subjects were evaluated at 2 or 4 week intervals for 11 months (15 visits). In addition to physical exams, blood counts and chemistry profiles, subjects had central lab evaluations [including measurements of red cell density (by Advia instrument), HbF, red cell cation content, KCl co-transport and Gardos channel activity, cell adhesion to endothelial cells and laminin, and erythrocyte membrane phosphatidyl serine (PS exposure)] at baseline (twice) and weeks 8, 16, 24, and 44. The primary endpoint was red cell density measured at week 8. Results. Forty-four subjects (median age 13.6 years, range 5-53, 73% < age 16) had baseline evaluations and were randomized, 36 reached the primary endpoint and 22 completed 11 months on study drugs. The trial was halted prematurely because of slow enrollment. Subjects in the HU groups (A and B) had increased red cell MCV, cell Hb and HbF compared to baseline and to groups C and D at week 8 (p Conclusions. HU had significant effects on HbSC erythrocytes, including increased HbF and MCV, with increasing response over 6 months. Mg at a dose of 0.6 mEq/kg/d had no measurable effect on red cell properties or endothelial interactions, either alone or in combination with HU. This may have been related to suboptimal dosing, since the maximum tolerated dose was recently found to be 0.9 mEq/kg/d. Differences in acute events, although not significant, suggest a need for studies with larger enrollment. These data provide a basis for performing clinical efficacy trials using HU, perhaps at higher doses, in subjects with HbSC disease. Disclosures: Off Label Use: Hydroxyurea is being tested for its effects on red blood cells in persons with HbSC disease. Magnesium pidolate is being tested for its effects on red blood cells in persons with HbSC disease.