{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:43:41Z","timestamp":1792597421209,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Children with SCD have elevated stroke risk, correlated with cerebral blood flow velocity (CBFV). HOPE Kids 2 was a phase 3, multicenter, double\u2010blind, placebo\u2010controlled trial evaluating the effect of voxelotor on CBFV. Participants aged 2 to &lt;\u200915\u2009years with SCD (HbSS\/HbS\u03b2\n                    <jats:sup>0<\/jats:sup>\n                    ) and conditional CBFV (170 to &lt;\u2009200\u2009cm\/s) were randomized 1:1 to voxelotor (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009120) or placebo (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009116) for 96\u2009weeks; 195 (83%) were in sub\u2010Saharan Africa. The primary endpoint, CBFV change from baseline to Week 24, was significantly greater with voxelotor (least\u2010squares mean change: voxelotor [\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009114] \u221212.06\u2009cm\/s, placebo [\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009108] \u22124.29\u2009cm\/s; difference \u22127.77\u2009cm\/s; 95% CI \u221213.18 to \u22122.37;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0048), with significant difference sustained through Week 48. Hemoglobin levels increased at Weeks 24 and 48 with voxelotor. Drug administration was paused in May 2024 when an imbalance of deaths was observed between treatment groups; subsequently, the trial discontinued when all active voxelotor trials were discontinued in September 2024. At study end, median (range) exposure was 84 (3\u2013104) weeks for voxelotor and 84 (3\u2013106) weeks for placebo. The most common SCD\u2010related treatment\u2010emergent adverse event was sickle cell anemia with crisis (voxelotor 59.2%; placebo 37.9%). All deaths (voxelotor\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098; placebo\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092) were considered unrelated to study drug by treating investigators. Overall, voxelotor showed CBFV reduction in children with SCD and conditional CBFV, suggesting HbS polymerization inhibition has a potential therapeutic role for this group; nevertheless, additional studies evaluating potential regional risks for sickle cell anemia with crisis or mortality are warranted.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04218084\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier: NCT04218084\n                  <\/jats:p>","DOI":"10.1002\/ajh.70457","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:30:21Z","timestamp":1787967021000},"page":"2799-2811","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>HOPE<\/scp>\n                    Kids 2: Phase 3, Randomized Trial of Voxelotor in Children With\n                    <scp>SCD<\/scp>\n                    and Conditional Cerebral Blood Flow Velocities"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9993-4548","authenticated-orcid":false,"given":"Halima","family":"Bello\u2010Manga","sequence":"first","affiliation":[{"name":"Barau Dikko Teaching Hospital Kaduna State University  Kaduna Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shehu Umar","family":"Abdullahi","sequence":"additional","affiliation":[{"name":"Aminu Kano Teaching Hospital Bayero University  Kano Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda","family":"Hassab","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biobele","family":"Brown","sequence":"additional","affiliation":[{"name":"University of Ibadan  Ibadan Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2266-8349","authenticated-orcid":false,"given":"Videlis","family":"Nduba","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research Kenya Medical Research Institute (KEMRI)  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie","family":"Githanga","sequence":"additional","affiliation":[{"name":"University of Nairobi  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-8511","authenticated-orcid":false,"given":"Adeseye Michael","family":"Akinsete","sequence":"additional","affiliation":[{"name":"College of Medicine University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"El\u2010Beshlawy","sequence":"additional","affiliation":[{"name":"Cairo University  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8967-273X","authenticated-orcid":false,"given":"Diana","family":"Hanna","sequence":"additional","affiliation":[{"name":"Zagazig University  Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4030-418X","authenticated-orcid":false,"given":"Catherine","family":"Segbefia","sequence":"additional","affiliation":[{"name":"University of Ghana Medical School  Accra Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iheanyi","family":"Okpala","sequence":"additional","affiliation":[{"name":"University of Nigeria Teaching Hospital  Ituku\u2010Ozalla Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza","family":"Tantawy","sequence":"additional","affiliation":[{"name":"Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhards","family":"Ogutu","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research Kenya Medical Research Institute (KEMRI)  Nairobi Kenya"},{"name":"CREATES, Strathmore University  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5973-8507","authenticated-orcid":false,"given":"Ven\u00e9e N.","family":"Tubman","sequence":"additional","affiliation":[{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8965-0549","authenticated-orcid":false,"given":"Vivian","family":"Paintsil","sequence":"additional","affiliation":[{"name":"Kwame Nkrumah University of Science and Technology  Kumasi Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4275-4524","authenticated-orcid":false,"given":"Yasser","family":"Wali","sequence":"additional","affiliation":[{"name":"College of Medicine and Health Sciences Sultan Qaboos University  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4860-0796","authenticated-orcid":false,"given":"Mohammed","family":"Essa","sequence":"additional","affiliation":[{"name":"King Abdullah Specialist Children's Hospital King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Ministry of National Guard  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-9184","authenticated-orcid":false,"given":"Paul","family":"Telfer","sequence":"additional","affiliation":[{"name":"Royal London Hospital, Barts Health NHS Trust 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Clark","family":"Brown","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the HOPE Kids 2 Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20103026(23)00118\u20107"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns5020020"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/09297049.2018.1526272"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.29943"},{"key":"e_1_2_12_6_1","volume-title":"Complications of SCD: Stroke","author":"Centers for Disease Control and Prevention 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