Hydroxyurea and Erythropoietin to Treat Sickle Cell Anemia
Status:
Completed
Trial end date:
2009-08-31
Target enrollment:
Participant gender:
Summary
This study will examine the use of hydroxyurea and erythropoietin for treating sickle cell
disease in patients who also have kidney disease or pulmonary hypertension (high blood
pressure in the lungs). Hydroxyurea increases production of fetal hemoglobin in the red blood
cells of patients with sickle cell disease, reducing the amount of sickle cells that cause
pain and other complications requiring hospitalizations. However, hydroxyurea treatment has
limitations: patients with sickle cell disease who have developed kidney disease may not be
able to get the full benefit of the medicine, and hydroxyurea alone may not be able to treat
life-threatening complications such as pulmonary hypertension or stroke. This study will
determine which of two dosing schedules of hydroxyurea and erythropoietin is more effective
for treating patients with sickle cell disease who also have kidney disease or pulmonary
hypertension, and will examine whether the two drugs can lower blood pressure in the lungs.
Patients 18 years of age and older with sickle cell anemia and kidney disease or pulmonary
hypertension, or both, may be eligible for this study. Candidates are screened with a medical
history, physical examination, blood tests, a 6-minute walk test (test to see how far the
subject can walk in 6 minutes), and echocardiogram (ultrasound of the heart to measure blood
pressure in the lungs).
Participants undergo the following tests and procedures:
Stabilization Phase: Patients take 2 hydroxyurea tablets a day until their fetal hemoglobin
levels stabilize, usually over 2 to 4 months. They have blood tests every 2 weeks to monitor
hemoglobin and fetal hemoglobin levels. At some time during this period, they undergo a test
to measure kidney function, in which they are injected with an iodine-containing dye and wear
a small pump for 1 day that injects a small amount of dye under the skin over 24 hours. They
come to the clinic for 2 or 3 blood tests collected over 4 hours.
Sequence I (Standard): When the fetal hemoglobin levels have been stable for 2 months,
patients have a repeat echocardiogram and 6-minute walk test. Erythropoietin is then added to
the hydroxyurea regimen. It is given 3 days a week, as an injection under the skin, along
with iron supplements. Patients have blood tests and blood pressure measurements every week
or every other week. Patients with pulmonary hypertension have another echocardiogram and
6-minute walk test once the hemoglobin level is stable.
Sequence II (Cycled): When hemoglobin levels have stabilized with hydroxyurea once a day and
erythropoietin 3 times a week, the hydroxyurea is adjusted so that the amount taken in 7 days
is "cycled" over 4 days, and the erythropoietin is cycled over 3 days, with the dose
increased twice, every 3 to 4 weeks. Blood pressure and hemoglobin are monitored once or
twice a month. Patients with pulmonary hypertension have another echocardiogram and 6-minute
walk test once the hemoglobin level is stable.
Patients who develop complications while taking the drugs have their treatment regimens
adjusted as needed.