Realizing effectiveness across continents with hydroxyurea: enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa
Despite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents w...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2018
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| _version_ | 1797079146065559552 |
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| author | McGann, PT Williams, TN Olupot-Olupot, P Tomlinson, GA Lane, A Luís Reis da Fonseca, J Kitenge, R Mochamah, G Wabwire, H Stuber, S Howard, TA McElhinney, K Aygun, B Latham, T Santos, B Tshilolo, L Ware, RE |
| author2 | REACH Investigators |
| author_facet | REACH Investigators McGann, PT Williams, TN Olupot-Olupot, P Tomlinson, GA Lane, A Luís Reis da Fonseca, J Kitenge, R Mochamah, G Wabwire, H Stuber, S Howard, TA McElhinney, K Aygun, B Latham, T Santos, B Tshilolo, L Ware, RE |
| author_sort | McGann, PT |
| collection | OXFORD |
| description | Despite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries. Following comprehensive training of local research teams, REACH was approved by local Ethics Committees and achieved full enrollment ahead of projections with 635 participants enrolled over a 30-month period, despite half of families living >12 km from their clinical site. At enrollment, study participants (age 5.4 ± 2.4 years) had substantial morbidity, including a history of vaso-occlusive pain (98%), transfusion (68%), malaria (85%), and stroke (6%). Significant differences in laboratory characteristics were noted across sites, with lower hemoglobin concentrations (P < .01) in Angola (7.2 ± 1.0 g/dL) and the DRC (7.0 ± 0.9 g/dL) compared to Kenya (7.4 ± 1.1 g/dL) and Uganda (7.5 ± 1.1 g/dL). Analysis of known genetic modifiers of SCA demonstrated a high frequency of α-thalassemia (58.4% with at least a single α-globin gene deletion) and G6PD deficiency (19.7% of males and 2.4% of females) across sites. The CAR β-globin haplotype was present in 99% of participants. The full enrollment to REACH confirms the feasibility of conducting high-quality SCA research in Africa; this study will provide vital information to guide safe and effective dosing of hydroxyurea for children with SCA living in Africa. |
| first_indexed | 2024-03-07T00:41:33Z |
| format | Journal article |
| id | oxford-uuid:83368959-63ea-4c94-92da-66bbffb12e29 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:41:33Z |
| publishDate | 2018 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:83368959-63ea-4c94-92da-66bbffb12e292022-03-26T21:42:48ZRealizing effectiveness across continents with hydroxyurea: enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan AfricaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:83368959-63ea-4c94-92da-66bbffb12e29EnglishSymplectic ElementsWiley2018McGann, PTWilliams, TNOlupot-Olupot, PTomlinson, GALane, ALuís Reis da Fonseca, JKitenge, RMochamah, GWabwire, HStuber, SHoward, TAMcElhinney, KAygun, BLatham, TSantos, BTshilolo, LWare, REREACH InvestigatorsDespite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries. Following comprehensive training of local research teams, REACH was approved by local Ethics Committees and achieved full enrollment ahead of projections with 635 participants enrolled over a 30-month period, despite half of families living >12 km from their clinical site. At enrollment, study participants (age 5.4 ± 2.4 years) had substantial morbidity, including a history of vaso-occlusive pain (98%), transfusion (68%), malaria (85%), and stroke (6%). Significant differences in laboratory characteristics were noted across sites, with lower hemoglobin concentrations (P < .01) in Angola (7.2 ± 1.0 g/dL) and the DRC (7.0 ± 0.9 g/dL) compared to Kenya (7.4 ± 1.1 g/dL) and Uganda (7.5 ± 1.1 g/dL). Analysis of known genetic modifiers of SCA demonstrated a high frequency of α-thalassemia (58.4% with at least a single α-globin gene deletion) and G6PD deficiency (19.7% of males and 2.4% of females) across sites. The CAR β-globin haplotype was present in 99% of participants. The full enrollment to REACH confirms the feasibility of conducting high-quality SCA research in Africa; this study will provide vital information to guide safe and effective dosing of hydroxyurea for children with SCA living in Africa. |
| spellingShingle | McGann, PT Williams, TN Olupot-Olupot, P Tomlinson, GA Lane, A Luís Reis da Fonseca, J Kitenge, R Mochamah, G Wabwire, H Stuber, S Howard, TA McElhinney, K Aygun, B Latham, T Santos, B Tshilolo, L Ware, RE Realizing effectiveness across continents with hydroxyurea: enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa |
| title | Realizing effectiveness across continents with hydroxyurea: enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa |
| title_full | Realizing effectiveness across continents with hydroxyurea: enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa |
| title_fullStr | Realizing effectiveness across continents with hydroxyurea: enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa |
| title_full_unstemmed | Realizing effectiveness across continents with hydroxyurea: enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa |
| title_short | Realizing effectiveness across continents with hydroxyurea: enrollment and baseline characteristics of the multicenter REACH study in Sub-Saharan Africa |
| title_sort | realizing effectiveness across continents with hydroxyurea enrollment and baseline characteristics of the multicenter reach study in sub saharan africa |
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