The proposed study is a randomized double-blind, placebo-controlled trial of hydroxyurea, to determine whether vaso-occlusive (painful) crisis rates in patients with sickle cell anemia can be reduced by at least 50%. Recurrent painful crises are the most disabling feature of the disease, interfering with education, vocational training, job retention and psychosocial development. Polymerization of sickle hemoglobin with deoxygenated red cells makes them rigid; vaso-occlusive lesions produced by nondeformable red cells are the cause of painful crises. Fetal hemoglobin (Hb F) interferes with polymerization. The recruitment goal is 286 patients; patients will be followed between 2 and 3 years. Hydroxyurea doses will be gradually increased from 15 mg/kg to the maximum level tolerated by each patient; placebo doses will be adjusted in a similar fashion. Patients and study personnel with direct patient contact will be blinded to treatment assignment. Each crisis reported will be reviewed by an independent committee to assure that it meets study criteria. The primary analysis will be a comparison of crisis attack rates in the treated and control groups. Secondary end point analyses will include comparison of changes in clinical status with changes in Hb F production, comparison of complications of sickle cell anemia in the two treatment groups, and frequency of non-compliance with either regimen. A clinical trial is necessary at this time because clinicians are already using hydroxyurea to treat sickle cell anemia, without proof of efficacy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01HL045696-01A1
Application #
3553472
Study Section
Clinical Trials Review Committee (CLTR)
Project Start
1991-05-22
Project End
1996-04-30
Budget Start
1991-05-22
Budget End
1992-04-30
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Maryland Medical Research Institute, Inc
Department
Type
DUNS #
069392181
City
Baltimore
State
MD
Country
United States
Zip Code
21210
Ballas, Samir K; Bauserman, Robert L; McCarthy, William F et al. (2010) The impact of hydroxyurea on career and employment of patients with sickle cell anemia. J Natl Med Assoc 102:993-9
Ballas, Samir K; Bauserman, Robert L; McCarthy, William F et al. (2010) Hydroxyurea and acute painful crises in sickle cell anemia: effects on hospital length of stay and opioid utilization during hospitalization, outpatient acute care contacts, and at home. J Pain Symptom Manage 40:870-82
Ballas, Samir K; McCarthy, William F; Guo, Nan et al. (2010) Early detection of response to hydroxyurea therapy in patients with sickle cell anemia. Hemoglobin 34:424-9
Ballas, Samir K; Barton, Franca B; Waclawiw, Myron A et al. (2006) Hydroxyurea and sickle cell anemia: effect on quality of life. Health Qual Life Outcomes 4:59
Moore, R D; Charache, S; Terrin, M L et al. (2000) Cost-effectiveness of hydroxyurea in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Am J Hematol 64:26-31
Steinberg, M H; Lu, Z H; Nagel, R L et al. (1998) Hematological effects of atypical and Cameroon beta-globin gene haplotypes in adult sickle cell anemia. Am J Hematol 59:121-6
McMahon, R P; Waclawiw, M A; Geller, N L et al. (1997) An extension of stochastic curtailment for incompletely reported and classified recurrent events: the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH). Control Clin Trials 18:420-30
Steinberg, M H; Lu, Z H; Barton, F B et al. (1997) Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter Study of Hydroxyurea. Blood 89:1078-88
Charache, S (1997) Mechanism of action of hydroxyurea in the management of sickle cell anemia in adults. Semin Hematol 34:15-21
Charache, S; Barton, F B; Moore, R D et al. (1996) Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive ""switching"" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine (Baltimore) 75:300-26

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