Hydroxyurea and Erythropoietin to Treat Sickle Cell Anemia

Completed · Phase 1

Conditions studied: Sickle Cell Disease, Chronic Kidney Disease, Pulmonary Hypertension

In brief

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.

Key facts

Study ID: NCT00270478
Run by: National Heart, Lung, and Blood Institute (NHLBI)
People needed: 7
Starts: 2005-12-21
Expected to finish: 2009-08-31
Last updated by the study team: 2019-12-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Patients who are doubly heterozygous for hemoglobin-S and fully or partially expressed hemoglobin-A or any other non-S beta-type globin chain, or hemoglobin A-only (non-sickle cell).
Patients who are on a chronic transfusion program, defined as regular transfusions every 2-8 weeks.
Patients who are pregnant or breast-feeding.
Patients who have a history of a documented cerebrovascular accident or venous thrombosis within one year of study entry.
Patients with active proliferative retinopathy within 1 year of study entry
Patients with eGFR less than or equal to 14 ml/min per 1.73 M(2) BSA.
Patients with a total Hgb at entry that is 10.5 g/dl or greater
Patients with a known allergy to Albumin or cell-derived products
Patients with uncontrolled hypertension, defined as a systolic blood pressure greater than 170 mmHg and diastolic blood pressure greater than 110 mm Hg that is sustained and unresponsive over 1 week to conventional anti-hypertensive therapy .

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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