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Daily Hydroxyurea Therapy Safe and Effective in Children With Sickle Cell Anemia, Authors Say

Off-label treatment studied in phase III trial

New data have shown that hydroxyurea therapy offers safe and effective disease management of sickle cell anemia (SCA) and reduces the risk of stroke, prompting early termination by the National Heart, Lung, and Blood Institute (NHLBI) of a key clinical trial studying the drug’s efficacy.

NHLBI officials issued the announcement November 19, about 1 year before the study was originally scheduled to end. Known as TWiTCH (TCD With Transfusions Changing to Hydroxyurea), the phase III randomized trial at 25 medical centers in the U.S. and Canada compared standard therapy (monthly erythrocyte transfusions) with the alternative (daily hydroxyurea) in children with elevated transcranial Doppler (TCD) velocities and a high risk of stroke.

“Early results indicate that TWiTCH is a success. Hydroxyurea works as well as blood transfusions to lower TCD velocities, which lowers the risk of the child having a stroke,” said principle investigator Russell E. Ware, MD, PhD.

“A group of outside experts has been reviewing the TWiTCH data every few months to ensure the safety of children in the clinical trial and to monitor the data,” Ware explained. “This group met recently and, after careful consideration of the interim data results, recommended that the study be stopped since hydroxyurea worked as well as transfusions to lower TCD velocities.” The NHLBI and the National Institutes of Health agreed with the recommendation.

The study enrolled its first patient in September 2011 and included children 4 to 16 years of age with SCA and abnormally elevated TCD velocities, which increased their risk of developing a stroke. The current standard of care for children with elevated TCD velocities is monthly blood transfusions. A total of 121 children were randomly assigned to receive either the standard therapy of transfusions or the alternate treatment with daily hydroxyurea, which is not approved for use in children with SCA.

The clinical data-collection portion of the study was originally scheduled for 24 months, but collection is being stopped early after only half of the children have completed the treatment phase, according to the authors.

“We did not know if hydroxyurea would reduce the risk of stroke as well as transfusions, so TWiTCH was an important research study,” said principal investigator Barry R. Davis, MD, PhD. “The study has now shown that hydroxyurea has a similar benefit as transfusions, so the study is closing early since the main research question has been answered.”

An important reason for testing hydroxyurea is that the current standard therapy of monthly blood transfusions to reduce the risk of stroke can lead to problems, such as antibody formation and iron overload, which are increasingly recognized as sources of morbidity in young patients with SCA.

During the past decade, the laboratory and clinical efficacy of hydroxyurea has been demonstrated in children and adults with SCA. Originally developed as a drug to treat cancer and infections, hydroxyurea boosts fetal hemoglobin production in SCA, which prevents red blood cells from acquiring the sickled shape that fuels the complications of the disease. Hydroxyurea has been shown to have clinical efficacy for many of these complications, but TWiTCH is the first phase III trial that demonstrated the treatment’s benefits for children with cerebrovascular disease and increased stroke risk, according to the investigators.

Source: PR Newswire; November 19, 2014.


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