title: Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial.
abstract: Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ(0) -thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0-35%) in the hydroxyurea arm and 47% (95% CI = 6-81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities.
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Hankins
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: McCarville
authors.affiliation: Sickle Cell Unit, Tropical Medicine Research Institute (TMRI), University of the West Indies, Kingston, Jamaica.
authors.forename: Angela
authors.initials: A
authors.lastname: Rankine-Mullings
authors.affiliation: Sickle Cell Unit, Tropical Medicine Research Institute (TMRI), University of the West Indies, Kingston, Jamaica.
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Reid
authors.affiliation: Instituto De Hematologia Arthur Siqueira Cavalcanti (HEMORIO), Rio De Janeiro, Brazil.
authors.forename: Clarisse L C
authors.initials: CL
authors.lastname: Lobo
authors.affiliation: Instituto De Hematologia Arthur Siqueira Cavalcanti (HEMORIO), Rio De Janeiro, Brazil.
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Moura
authors.affiliation: Sickle Cell Unit, Tropical Medicine Research Institute (TMRI), University of the West Indies, Kingston, Jamaica.
authors.forename: Susanna
authors.initials: S
authors.lastname: Ali
authors.affiliation: Sickle Cell Unit, Tropical Medicine Research Institute (TMRI), University of the West Indies, Kingston, Jamaica.
authors.forename: Deanne P
authors.initials: DP
authors.lastname: Soares
authors.affiliation: Sickle Cell Unit, Tropical Medicine Research Institute (TMRI), University of the West Indies, Kingston, Jamaica.
authors.forename: Karen
authors.initials: K
authors.lastname: Aldred
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Jay
authors.affiliation: Division of Pediatric Hematology/Oncology and Stem Cell Transplantation, Cohen Children's Medical Center of New York, New Hyde Park, New York.
authors.forename: Banu
authors.initials: B
authors.lastname: Aygun
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: John
authors.initials: J
authors.lastname: Bennett
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Guolian
authors.initials: G
authors.lastname: Kang
authors.affiliation: National Heart Lung and Blood Institute, Bethesda, Maryland.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Goldsmith
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Smeltzer
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.affiliation: Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D000970:Antineoplastic Agents; D006918:Hydroxyurea