Conclusive data showing that hydroxyurea therapy reduces stroke risks for children with sickle cell anemia and provides other benefits prompted the National Heart Lung and Blood Institute (NHLBI) to end a major clinical trial of the treatment in November 2014, about one year ahead of schedule.

Since 2011, more than 120 children aged 4 to 16 had enrolled in the Phase III clinical study entitled TWiTCH (TCD With Transfusions Changing to Hydroxyurea). Experts at 25 medical centers in the U.S. and Canada compared the effects of standard, monthly blood transfusions to daily doses of hydroxyurea.

"Early results indicate that TWiTCH is a success. Hydroxyurea works as well as blood transfusions to lower Transcranial Doppler (TCD) velocities, which lowers the risk of the child having a stroke," said Russell Ware, MD, PhD, the study’s principal investigator and director of Hematology at Cincinnati Children's.

Drug reduces stroke risk

The ability to rely on hydroxyurea to reduce stroke risk is important because standard blood transfusions can lead to antibody formation and iron overload, which are increasingly recognized as health threats to young patients with sickle cell disease.

Hydroxyurea was originally developed as a cancer treatment. In sickle cell, the drug boosts fetal hemoglobin production, which prevents red blood cells from acquiring the sickle shape that causes organ damage and frequent bouts of pain. Although other studies have shown that the drug reduces a variety of sickle-related complications, this was the first large clinical trial to confirm stroke reduction benefits.

 "No child should ever suffer a stroke, which is why it was so important for the NHLBI to support the TWiTCH trial," said Gary Gibbons, MD, director of the NHLBI, in a statement to the media. "This critical research finding opens the door to more treatment options for clinicians trying to prevent strokes in children living with sickle cell disease."

Treatment standards change

The end of the clinical trial occurred just two months after health leaders called for major changes in recommended treatment approaches for sickle cell disease. In September, an expert panel formed by the NHLBI “strongly recommended” hydroxyurea and transfusion therapy for patients with sickle cell disease. The panel’s new treatment guidelines were published Sept. 10, 2014, in JAMA.

Among the changes, hydroxyurea therapy is recommended for:

  • Any adult who has had three or more severe vasooclusive crises within one year
  • Patients with sickle cell disease pain or chronic, debilitating anemia
  • Patients with severe or chronic acute chest syndrome
  •  Infants, children and adolescents regardless of the presence of severe symptoms