The use of combination chemotherapy has been developed successfully over several decades for the treatment of? cancer and, more recently, HIV infection. However, the principles of treatment with multiple drugs which have? distinct and additive or synergistic mechanisms of action and non-overlapping toxicity have not been applied to? the treatment of sickle cell disease. The primary' hypothesis to be addressed in the Network (Inter-Center)? Study is that combination treatment with hydroxyurea and magnesium will have a greater effect on the? prevention of vaso-occlusive complications of sickle cell disease than treatment with hydroxyurea alone.? Therefore, the Network Study will address Specific Aim 1: To determine the efficacy of combination? treatment with hydroxyurea and magnesium compared to treatment with hydroxyurea alone on painful? events and episodes of acute chest syndrome through Phase IIl trials in children and adults with sickle? cell disease. Two separate, randomized double-blinded, multi-institutional trials of hydroxyurea and? magnesium versus hydroxyurea and placebo will be conducted. Study I will enroll newly treated, symptomatic? patients who meet the criteria for severe disease. Randomization to magnesium or placebo will occur after six? months of hydroxyurea treatment during which time the maximal tolerated dose will be defined for each patient.? Study II will enroll patients who have been previously treated with hydroxyurea for a minimum of 12 months? but who remain symptomatic as reflected by the occurrence of a vaso-occlusive crisis within the 12 months prior? to enrollment.
Specific Aim 2 : To measure splenic function by liver-spleen scan in patients treated on the? Phase III trials prior to randomization and after two years of treatment. Little information is available? with respect to the impact of drug therapy on spleen structure and function. By systematically collecting data,? we will be able to compare the frequency of restoration of spleen function as reflected by the liver-spleen scan in children and adults treated with hydroxyurea alone or hydroxyurea and magnesium. At the completion of these? Network (Inter-Center) trials, we will know whether the combination of hydroxyurea and magnesium is superior? to hydroxyurea alone in the prevention of vaso-occlusive events and we will have preliminary information? the frequency with which hydroxyurea or hydroxyurea/magnesium can restore splenic function.
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