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Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial

Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial
Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial

Strokes in children with sickle cell anemia (SCA) are associated with significant morbidity and premature death. Primary stroke prevention in children with SCA involves screening for abnormal transcranial Doppler (TCD) velocity coupled with regular blood transfusion therapy for children with abnormal velocities, for at least one year. However, in Africa, where the majority of children with SCA live, regular blood transfusions are not feasible due to inadequate supply of safe blood, cost, and the reluctance of caregivers to accept transfusion therapy for their children. We describe the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria Trial [StrokePreventioninNigeria (SPRING) trial, NCT02560935], a three-center double-blinded randomized controlled Phase III clinical trial to 1) determine the efficacy of moderate fixed-dose (20 mg/kg/day) versus low fixed-dose (10 mg/kg/day) hydroxyurea therapy for primary stroke prevention; 2) determine the efficacy of moderate fixed-dose hydroxyurea for decreasing the incidence of all cause-hospitalization (pain, acute chest syndrome, infection, other) compared to low fixed-dose hydroxyurea. We will test the primary hypothesis that there will be a 66% relative risk reduction of strokes in children with SCA and abnormal TCD measurements, randomly allocated, for a minimum of three years to receive moderate fixed-dose versus low fixed-dose hydroxyurea (total n = 220). The results of this trial will advance the care of children with SCA in sub-Saharan Africa, while improving research capacity for future studies to prevent strokes in children with SCA.

Hydroxyurea, primary stroke prevention, sickle cell anemia, Sub-Saharan Africa
0888-0018
1-17
Abdullahi, Shehu U.
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Wudil, Binta J.
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Bello-Manga, Halima
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Musa, Aisha B.
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Gambo, Safiya
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Galadanci, Najibah A.
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Aminu, Hauwa
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Tijjani Gaya, Aliyu
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Sanusi, Surayya
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Tabari, Musa A.
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Galadanci, Aisha
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Borodo, Awwal
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Abba, Muhammed S.
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Dambatta, Abdu H.
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Haliru, Lawal
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Gambo, Awwal
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Cassell, Holly
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Rodeghier, Mark
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Ghafuri, Djamila L.
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Covert Greene, Brittany V.
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Neville, Kathleen
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Kassim, Adetola A.
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Kirkham, Fenella
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Trevathan, Edwin
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Jordan, Lori C.
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Aliyu, Muktar H.
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DeBaun, Michael R.
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Abdullahi, Shehu U.
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Wudil, Binta J.
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Bello-Manga, Halima
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Musa, Aisha B.
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Gambo, Safiya
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Galadanci, Najibah A.
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Aminu, Hauwa
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Tijjani Gaya, Aliyu
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Sanusi, Surayya
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Tabari, Musa A.
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Galadanci, Aisha
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Borodo, Awwal
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Abba, Muhammed S.
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Dambatta, Abdu H.
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Haliru, Lawal
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Gambo, Awwal
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Cassell, Holly
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Rodeghier, Mark
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Ghafuri, Djamila L.
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Covert Greene, Brittany V.
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Neville, Kathleen
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Kassim, Adetola A.
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Kirkham, Fenella
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Trevathan, Edwin
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Jordan, Lori C.
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Aliyu, Muktar H.
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DeBaun, Michael R.
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Abdullahi, Shehu U., Wudil, Binta J., Bello-Manga, Halima, Musa, Aisha B., Gambo, Safiya, Galadanci, Najibah A., Aminu, Hauwa, Tijjani Gaya, Aliyu, Sanusi, Surayya, Tabari, Musa A., Galadanci, Aisha, Borodo, Awwal, Abba, Muhammed S., Dambatta, Abdu H., Haliru, Lawal, Gambo, Awwal, Cassell, Holly, Rodeghier, Mark, Ghafuri, Djamila L., Covert Greene, Brittany V., Neville, Kathleen, Kassim, Adetola A., Kirkham, Fenella, Trevathan, Edwin, Jordan, Lori C., Aliyu, Muktar H. and DeBaun, Michael R. (2020) Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial. Pediatric Hematology and Oncology, 1-17. (doi:10.1080/08880018.2020.1810183).

Record type: Article

Abstract

Strokes in children with sickle cell anemia (SCA) are associated with significant morbidity and premature death. Primary stroke prevention in children with SCA involves screening for abnormal transcranial Doppler (TCD) velocity coupled with regular blood transfusion therapy for children with abnormal velocities, for at least one year. However, in Africa, where the majority of children with SCA live, regular blood transfusions are not feasible due to inadequate supply of safe blood, cost, and the reluctance of caregivers to accept transfusion therapy for their children. We describe the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria Trial [StrokePreventioninNigeria (SPRING) trial, NCT02560935], a three-center double-blinded randomized controlled Phase III clinical trial to 1) determine the efficacy of moderate fixed-dose (20 mg/kg/day) versus low fixed-dose (10 mg/kg/day) hydroxyurea therapy for primary stroke prevention; 2) determine the efficacy of moderate fixed-dose hydroxyurea for decreasing the incidence of all cause-hospitalization (pain, acute chest syndrome, infection, other) compared to low fixed-dose hydroxyurea. We will test the primary hypothesis that there will be a 66% relative risk reduction of strokes in children with SCA and abnormal TCD measurements, randomly allocated, for a minimum of three years to receive moderate fixed-dose versus low fixed-dose hydroxyurea (total n = 220). The results of this trial will advance the care of children with SCA in sub-Saharan Africa, while improving research capacity for future studies to prevent strokes in children with SCA.

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Accepted/In Press date: 26 July 2020
e-pub ahead of print date: 25 November 2020
Keywords: Hydroxyurea, primary stroke prevention, sickle cell anemia, Sub-Saharan Africa

Identifiers

Local EPrints ID: 446122
URI: http://eprints.soton.ac.uk/id/eprint/446122
ISSN: 0888-0018
PURE UUID: fc49ac02-38db-4ade-b9a7-caba62704eb0
ORCID for Fenella Kirkham: ORCID iD orcid.org/0000-0002-2443-7958

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Date deposited: 21 Jan 2021 17:33
Last modified: 17 Mar 2024 06:09

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Contributors

Author: Shehu U. Abdullahi
Author: Binta J. Wudil
Author: Halima Bello-Manga
Author: Aisha B. Musa
Author: Safiya Gambo
Author: Najibah A. Galadanci
Author: Hauwa Aminu
Author: Aliyu Tijjani Gaya
Author: Surayya Sanusi
Author: Musa A. Tabari
Author: Aisha Galadanci
Author: Awwal Borodo
Author: Muhammed S. Abba
Author: Abdu H. Dambatta
Author: Lawal Haliru
Author: Awwal Gambo
Author: Holly Cassell
Author: Mark Rodeghier
Author: Djamila L. Ghafuri
Author: Brittany V. Covert Greene
Author: Kathleen Neville
Author: Adetola A. Kassim
Author: Fenella Kirkham ORCID iD
Author: Edwin Trevathan
Author: Lori C. Jordan
Author: Muktar H. Aliyu
Author: Michael R. DeBaun

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