MUSC researchers part of terminated NIH sickle cell study

New therapy shows promising results, offers paradigm shift for high-risk patients

CHARLESTON, SC – A study involving MUSC sickle cell anemia researchers Robert Adams, M.D., and Sherron M. Jackson, M.D., has been stopped early due to conclusive data that showed hydroxyurea therapy offers safe and effective disease management of sickle cell anemia (SCA) and reduces the risk of stroke. The early termination of this key clinical trial studying the drug’s efficacy was issued by the National Heart Lung and Blood Institute (NHLBI) about one year ahead of when it was originally scheduled to end.

Going by the title TWiTCH (TCD With Transfusions Changing to Hydroxyurea), the Phase III randomized clinical trial at 25 medical centers in the U.S. and Canada compared standard therapy (monthly erythrocyte transfusions) with the alternative (daily hydroxyurea) for children with elevated transcranial Doppler (TCD) velocities and high risk of stroke.

“This signals a paradigm shift in treating children with sickle cell anemia who are at risk for stroke,” said Adams, South Carolina Centers of Economic Excellence for Stroke endowed chair and director, and co-principal investigator for the study’s neurological core. “We are moving from stroke prevention to vascular protection, with screening early and often for the risk factors of stroke in these patients. We’ve been working on this for decades and it’s gratifying to see this work come to fruition. We have an incredible opportunity to offer a less complicated and invasive therapy that can reduce the likelihood of stroke in these patients and improve the health of their blood vessels, too.”

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

According to Russell E. Ware, M.D., Ph.D, principal investigator of the larger study and director of Hematology at Cincinnati Children’s Hospital Medical Center, which served as the study’s medical coordinating center, these 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,” he said. “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. 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 study enrolled its first patient in September 2011 and included children between ages 4 and 16 years with sickle cell anemia and abnormally elevated TCD velocities, which increases their risk of developing a stroke. The current standard therapy for children with elevated TCD velocities is monthly blood transfusions. A total of 121 children were randomized: half received the standard therapy of transfusions while the other half received the alternate treatment with daily hydroxyurea, which has not yet been approved for children with sickle cell anemia.

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 the red blood cells from acquiring the sickled shape that fuels the many complications. Hydroxyurea has been previously shown to have clinical efficacy for a variety of sickle-related complications, but TWiTCH is the first Phase III trial that demonstrates its benefits for children with cerebrovascular disease and increased stroke risk.

About MUSC

Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $1.7 billion. MUSC operates a 750-bed medical center, which includes a nationally recognized Children’s Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (one of 66 National Cancer Institute designated centers) Level I Trauma Center and Institute of Psychiatry. For more information on academic information or clinical services, visit www.musc.edu.