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TCD with Transfusions Changing to Hydroxyurea (TWiTCH): Hydroxyurea Therapy As an Alternative to Transfusions for Primary Stroke Prevention in Children with Sickle Cell Anemia

TCD with Transfusions Changing to Hydroxyurea (TWiTCH): Hydroxyurea Therapy As an Alternative to Transfusions for Primary Stroke Prevention in Children with Sickle Cell Anemia

Authors :
Jennifer A. Rothman
Kerri Nottage
Kathleen J. Helton
William Owen
Margaret T. Lee
Beng Fuh
Robert J. Adams
Cynthia Gauger
Peng Wei
Linda B. Piller
Carla W. Roberts
William H. Schultz
Abdullah Kutlar
Banu Aygun
John C. Wood
Russell E. Ware
Melanie J. Bonner
Lee Hilliard
Niren Patel
Janet L. Kwiatkowski
Isaac Odame
Susan E. Stuber
Zora R. Rogers
Alexis A. Thompson
Barry R. Davis
Sherron M. Jackson
Hamayun Imran
Scott T. Miller
Donna R. Roberts
Theodosia A. Kalfa
Alex George
Lori Luchtman-Jones
Sharada A. Sarnaik
Nicole A. Mortier
Stephen C. Nelson
Alan R. Cohen
Connie M. Piccone
Naomi L.C. Luban
Jamie L. Coleman
Judy Luden
Sara L. Pressel
Ofelia A. Alvarez
Melissa Rhodes
Clark Brown
Matthew M. Heeney
Source :
Blood. 126:3-3
Publication Year :
2015
Publisher :
American Society of Hematology, 2015.

Abstract

Transcranial Doppler (TCD) screening in children with sickle cell anemia (SCA) identifies abnormally elevated cerebral artery flow velocities that confer an elevated risk for primary stroke. Chronic transfusions offer effective stroke prophylaxis in this setting, but must be continued indefinitely and lead to transfusional iron overload. An alternative treatment strategy that offers similar effective protection against primary stroke, and provides control of iron overload, is needed. TCD With Transfusions Changing to Hydroxyurea (TWiTCH, NCT01425307) was an NHLBI-funded Phase III multicenter randomized clinical trial comparing 24-months of standard treatment (transfusions) to alternative treatment (hydroxyurea) in children with SCA and abnormal TCD velocities. All eligible children had received at least 12 months of transfusions. TWiTCH had a non-inferiority trial design; the primary study endpoint was the 24-month TCD velocity obtained from a linear mixed model, controlling for baseline (enrollment) values, with a non-inferiority margin of 15 cm/sec. The transfusion arm maintained children at HbS 240 cm/sec. Exit brain MRI/MRA exams documented no new parenchymal abnormalities but one child (transfusion arm) developed new vasculopathy. Sickle cell related serious adverse events were more common in the hydroxyurea arm than the transfusion arm (23 to 15), but none was related to study treatment or study procedures. Iron overload improved more in the hydroxyurea arm than in the transfusion arm, with a greater average change in serum ferritin (-1085 compared to -38 ng/mL, p Disclosures Ware: Eli Lilly: Other: DSMB membership; Bayer Pharmaceuticals: Consultancy; Bristol Myers Squibb: Research Funding; Biomedomics: Research Funding. Off Label Use: Hydroxyurea for children with SCA. Owen:Novartis: Speakers Bureau. Rogers:BioRad Labs: Consultancy; Apopharma: Consultancy; Baxter: Consultancy; Glaxo Smith Kline: Consultancy. Kwiatkowski:Shire Pharmaceuticals and Sideris Pharmaceuticals: Consultancy; Sideris Pharmaceuticals: Consultancy; Novartis: Research Funding; ISIS: Membership on an entity's Board of Directors or advisory committees. Heeney:Sancillio: Consultancy; Eli Lilly: Research Funding. Nottage:Janssen Pharmaceuticals: Employment. Cohen:Novartis: Consultancy; ApoPharma: Other: DSMB member.

Details

ISSN :
15280020, 00064971, and 01425307
Volume :
126
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi...........78eaefcb9dad7215762a3ebb41e48b3b
Full Text :
https://doi.org/10.1182/blood.v126.23.3.3