Stroke With Transfusions Changing to Hydroxyurea (SWiTCH)
Russell E Ware, Ronald W Helms, SWiTCH Investigators, Brigitta U Mueller, Bogdan Dinu, Matthew Heeney, Meredith Anderson, Amber Smith, Tiffany Kang, Janet L Kwiatkowski, Kim Smith-Whitley, Jeffrey Olson, Vanessa Nixon, LaVerne Murphy, Lakshmanan Krishnamurti, Regina McCollum, Alexis Thompson, Jillian Prado, Kelly Verel, Ashley Brummel, Gerald Woods, Julie Routhieaux, Anne Mehrhof, Kristin Stegenga, Lori Luchtman-Jones, Caterina Minniti, Sheronda D Brown, Tracy Boswell, Ryan Burnett, Karen Kalinyak, Laurie Vanderah, Monique Lumpkin, Tammy Nordheim, Sharon Singh, Ellen Muir, Margaret T Lee, Genia Billote, Charles Daeschner, Diana Wyn Gordon, Cynthia Brown, William Owen, Anthony Villella, Terri Forsyth, Annette Slade, Lorrie Coggsdale, Clark Brown, Ifeyinwa Osunkwo, Peter Lane, Brian Philbrook, Terrell Faircloth, Korin Cherry, Elizabeth Record, Eldrida Carter Randall, Ann Martha Felder, James Rhodes, Paul Scott, Danielle Jirovec, Lindsey Nelson, Sherron M Jackson, Mary Ellen Cavalier, Lisa Kuisel, Jessica Peterson, Betsy Rackoff, Cynthia Gauger, Mary Warde, Ramamoorthy Nagasubramanian, Leslie Natal, Dawn Cook, Rafael Barilari, JoAnne Neville, Banu Aygun, Winfred C Wang, Eileen Hansbury, Jennifer Larkin, Laura Martino, Lane Faughnan, Scott Miller, Kathy Rey, Lezlie Woods, Catherine Driscoll, Lakeisha N Nicholls, Zora R Rogers, Leah Adix, Roxana Mars, Brad Cook, Jennifer Marshall, Lee Hilliard, Jeanine Dumas, Lindley Webb, Annelle Reed, Ofelia Alvarez, Tally Hustace, Patrice Williams, Mary Donovan, Rathi Iyer, Mary Gail Smith, Stephanie Pepper, Glenda Thomas, Gloria Bishop, Cindy Kendig, Teresa Walker, Elizabeth Yang, Lesley Ann Owen, Sharada Sarnaik, Mary Murphy, Cynthia Burnett, Clarissa Shavers, Russell E Ware, Ronald W Helms, SWiTCH Investigators, Brigitta U Mueller, Bogdan Dinu, Matthew Heeney, Meredith Anderson, Amber Smith, Tiffany Kang, Janet L Kwiatkowski, Kim Smith-Whitley, Jeffrey Olson, Vanessa Nixon, LaVerne Murphy, Lakshmanan Krishnamurti, Regina McCollum, Alexis Thompson, Jillian Prado, Kelly Verel, Ashley Brummel, Gerald Woods, Julie Routhieaux, Anne Mehrhof, Kristin Stegenga, Lori Luchtman-Jones, Caterina Minniti, Sheronda D Brown, Tracy Boswell, Ryan Burnett, Karen Kalinyak, Laurie Vanderah, Monique Lumpkin, Tammy Nordheim, Sharon Singh, Ellen Muir, Margaret T Lee, Genia Billote, Charles Daeschner, Diana Wyn Gordon, Cynthia Brown, William Owen, Anthony Villella, Terri Forsyth, Annette Slade, Lorrie Coggsdale, Clark Brown, Ifeyinwa Osunkwo, Peter Lane, Brian Philbrook, Terrell Faircloth, Korin Cherry, Elizabeth Record, Eldrida Carter Randall, Ann Martha Felder, James Rhodes, Paul Scott, Danielle Jirovec, Lindsey Nelson, Sherron M Jackson, Mary Ellen Cavalier, Lisa Kuisel, Jessica Peterson, Betsy Rackoff, Cynthia Gauger, Mary Warde, Ramamoorthy Nagasubramanian, Leslie Natal, Dawn Cook, Rafael Barilari, JoAnne Neville, Banu Aygun, Winfred C Wang, Eileen Hansbury, Jennifer Larkin, Laura Martino, Lane Faughnan, Scott Miller, Kathy Rey, Lezlie Woods, Catherine Driscoll, Lakeisha N Nicholls, Zora R Rogers, Leah Adix, Roxana Mars, Brad Cook, Jennifer Marshall, Lee Hilliard, Jeanine Dumas, Lindley Webb, Annelle Reed, Ofelia Alvarez, Tally Hustace, Patrice Williams, Mary Donovan, Rathi Iyer, Mary Gail Smith, Stephanie Pepper, Glenda Thomas, Gloria Bishop, Cindy Kendig, Teresa Walker, Elizabeth Yang, Lesley Ann Owen, Sharada Sarnaik, Mary Murphy, Cynthia Burnett, Clarissa Shavers
Abstract
Stroke is a devastating complication of sickle cell anemia (SCA) with high recurrence if untreated. Chronic transfusions reduce recurrent strokes but have associated morbidities including iron overload. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) was a multicenter phase 3 randomized trial comparing standard treatment (transfusions/chelation) to alternative treatment (hydroxyurea/phlebotomy) for children with SCA, stroke, and iron overload. SWiTCH was a noninferiority trial with a composite primary end point, allowing an increased stroke risk but requiring superiority for removing iron. Subjects on standard treatment received monthly transfusions plus daily deferasirox iron chelation. Subjects on alternative treatment received hydroxyurea plus overlap transfusions during dose escalation to maximum tolerated dose (MTD), followed by monthly phlebotomy. Subjects on standard treatment (N = 66) maintained 30% sickle hemoglobin (HbS) and tolerated deferasirox at 28.2 ± 6.0 mg/kg/d. Subjects on alternative treatment (N = 67) initiated hydroxyurea and 60 (90%) reached MTD at 26.2 ± 4.9 mg/kg/d with 29.1% ± 6.7% fetal hemoglobin (HbF). Adjudication documented no strokes on transfusions/chelation but 7 (10%) on hydroxyurea/phlebotomy, still within the noninferiority stroke margin. The National Heart, Lung, and Blood Institute closed SWiTCH after interim analysis revealed equivalent liver iron content, indicating futility for the composite primary end point. Transfusions and chelation remain a better way to manage children with SCA, stroke, and iron overload.
Trial registration: ClinicalTrials.gov NCT00122980.
Figures
Source: PubMed