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Acceptability and safety of hydroxyurea for primary prevention of stroke in children with sickle cell disease in Nigeria

Acceptability and safety of hydroxyurea for primary prevention of stroke in children with sickle cell disease in Nigeria
Acceptability and safety of hydroxyurea for primary prevention of stroke in children with sickle cell disease in Nigeria
Background: Nigeria has the highest prevalence of sickle cell disease (SCD), a common cause of pediatric ischemic stroke. In sub-Saharan Africa monthly blood transfusions for primary stroke prevention carries risks; hydroxyurea (HU) may be an alternative. We conducted the first, US NIH funded, SCD feasibility trial in sub-Saharan Africa (5R21NS080639-02) to: 1) assess the acceptability and willingness of families to participate in a HU trial; 2) develop a safety protocol for using HU in a trial setting in sub-Saharan Africa; and 3) prepare for a definitive phase III Trial. In the Sickle Cell Disease Stroke Prevention in Nigeria (SPIN) trial, our primary hypothesis in the internal feasibility trial is that 80% adherence for daily HU administration is feasible. Procedure: The internal pilot is a single site; single arm trial enrolling 40 children aged 5 to 12 years with hemoglobin SS or SB0 thalassemia at risk of developing stroke with a high transcranial Doppler (TCD) velocity in the middle cerebral artery (MCA) ≥ 200 cm/sec. Each participant is scheduled to receive low dose HU therapy (~20mg/kg/day) for 36 months. Acceptability was determined by the number of families who consented for screening. The adherence rate of HU was based on monthly parental assessment of the Morisky Medical Adherence Sore (MMAS) and monthly complete blood count (CBC) to monitor the serial change in mean corpuscular volume (MCV) from baseline level. Assessment of toxicity attributable to HU was based on comparing adverse events between the HU and control groups. Controls were identified as participants that met the criteria for the trial, but had TCD measurements < 200 cm/sec. From Baby HUG, adverse events were defined as hospitalization for any cause, severe anemia and myelosuppression (severe neutropenia and thrombocytopenia based on monthly CBC). Results: A total of 269 participants were approached, of which 96% (23 of 24) and 86% (211 of 245) with an elevated or normal TCD measurement agreed to enroll in the HU therapy or control groups with a median age of 8 and 7.6 years, respectively. At the current milestone, 100% of the participants enrolled in the treatment arm demonstrated at least average to high monthly adherence rate (MMAS of 6-8 points). This adherence rate was consistent with an increase in MCV from baseline to 3 months after starting HU therapy with a minimum increase in MCV of at least 3 fl in 8 of 11 participants. One child on HU therapy was hospitalized for 5 days for hypovolemia and dehydration associated with cholera. The table below shows no excessive rate of adverse events when HU therapy and control groups are compared. Conclusion: These early results demonstrate the ability for a sub-Saharan African clinical research team to plan and initiate a complex SCD trial. Our preliminary data provide strong evidence for acceptability and potential safety of low dose HU therapy in Nigerian children with SCD. Completion of the internal pilot should provide sufficient evidence to pursue a phase III trial of low dose HU therapy to prevent strokes in children living in sub-Saharan Africa.
0006-4971
4021
DeBaun, Michael R.
76559153-80c6-4642-bdf8-672a75570dfe
Galadanci, Najibah Aliyu
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Abdullahi, Shehu U.
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Tabari, Musa A.
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Abubakar, Shehi
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Belonwu, Raymond
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Salihu, Auwal
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Neville, Kathleen A.
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Kirkham, Fenella J.
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Inusa, Baba P. D.
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Shyr, Yu
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Phillips, Sharon
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Kassim, Adetola A.
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Jordan, Lori C.
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Aliyu, Muktar H.
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Covert, Brittany V.
fe5cd779-28e7-4822-93d7-bd2c0b7bc505
DeBaun, Michael R.
76559153-80c6-4642-bdf8-672a75570dfe
Galadanci, Najibah Aliyu
520d8472-2632-49ee-af02-8e83bbd49f4b
Abdullahi, Shehu U.
989cd144-48e5-4d6a-a37f-1b9cc39a6354
Tabari, Musa A.
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Abubakar, Shehi
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Belonwu, Raymond
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Salihu, Auwal
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Neville, Kathleen A.
3498c018-d41a-4aab-babd-dcad91a80e66
Kirkham, Fenella J.
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Inusa, Baba P. D.
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Shyr, Yu
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Phillips, Sharon
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Kassim, Adetola A.
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Jordan, Lori C.
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Aliyu, Muktar H.
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Covert, Brittany V.
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DeBaun, Michael R., Galadanci, Najibah Aliyu, Abdullahi, Shehu U., Tabari, Musa A., Abubakar, Shehi, Belonwu, Raymond, Salihu, Auwal, Neville, Kathleen A., Kirkham, Fenella J., Inusa, Baba P. D., Shyr, Yu, Phillips, Sharon, Kassim, Adetola A., Jordan, Lori C., Aliyu, Muktar H. and Covert, Brittany V. (2014) Acceptability and safety of hydroxyurea for primary prevention of stroke in children with sickle cell disease in Nigeria. Blood, 124 (21), 4021.

Record type: Article

Abstract

Background: Nigeria has the highest prevalence of sickle cell disease (SCD), a common cause of pediatric ischemic stroke. In sub-Saharan Africa monthly blood transfusions for primary stroke prevention carries risks; hydroxyurea (HU) may be an alternative. We conducted the first, US NIH funded, SCD feasibility trial in sub-Saharan Africa (5R21NS080639-02) to: 1) assess the acceptability and willingness of families to participate in a HU trial; 2) develop a safety protocol for using HU in a trial setting in sub-Saharan Africa; and 3) prepare for a definitive phase III Trial. In the Sickle Cell Disease Stroke Prevention in Nigeria (SPIN) trial, our primary hypothesis in the internal feasibility trial is that 80% adherence for daily HU administration is feasible. Procedure: The internal pilot is a single site; single arm trial enrolling 40 children aged 5 to 12 years with hemoglobin SS or SB0 thalassemia at risk of developing stroke with a high transcranial Doppler (TCD) velocity in the middle cerebral artery (MCA) ≥ 200 cm/sec. Each participant is scheduled to receive low dose HU therapy (~20mg/kg/day) for 36 months. Acceptability was determined by the number of families who consented for screening. The adherence rate of HU was based on monthly parental assessment of the Morisky Medical Adherence Sore (MMAS) and monthly complete blood count (CBC) to monitor the serial change in mean corpuscular volume (MCV) from baseline level. Assessment of toxicity attributable to HU was based on comparing adverse events between the HU and control groups. Controls were identified as participants that met the criteria for the trial, but had TCD measurements < 200 cm/sec. From Baby HUG, adverse events were defined as hospitalization for any cause, severe anemia and myelosuppression (severe neutropenia and thrombocytopenia based on monthly CBC). Results: A total of 269 participants were approached, of which 96% (23 of 24) and 86% (211 of 245) with an elevated or normal TCD measurement agreed to enroll in the HU therapy or control groups with a median age of 8 and 7.6 years, respectively. At the current milestone, 100% of the participants enrolled in the treatment arm demonstrated at least average to high monthly adherence rate (MMAS of 6-8 points). This adherence rate was consistent with an increase in MCV from baseline to 3 months after starting HU therapy with a minimum increase in MCV of at least 3 fl in 8 of 11 participants. One child on HU therapy was hospitalized for 5 days for hypovolemia and dehydration associated with cholera. The table below shows no excessive rate of adverse events when HU therapy and control groups are compared. Conclusion: These early results demonstrate the ability for a sub-Saharan African clinical research team to plan and initiate a complex SCD trial. Our preliminary data provide strong evidence for acceptability and potential safety of low dose HU therapy in Nigerian children with SCD. Completion of the internal pilot should provide sufficient evidence to pursue a phase III trial of low dose HU therapy to prevent strokes in children living in sub-Saharan Africa.

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Published date: 6 December 2014

Identifiers

Local EPrints ID: 424292
URI: http://eprints.soton.ac.uk/id/eprint/424292
ISSN: 0006-4971
PURE UUID: bf874b3e-7e8a-4c4c-a02e-a61054dee98a
ORCID for Fenella J. Kirkham: ORCID iD orcid.org/0000-0002-2443-7958

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Date deposited: 05 Oct 2018 11:35
Last modified: 23 Jul 2022 01:48

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Contributors

Author: Michael R. DeBaun
Author: Najibah Aliyu Galadanci
Author: Shehu U. Abdullahi
Author: Musa A. Tabari
Author: Shehi Abubakar
Author: Raymond Belonwu
Author: Auwal Salihu
Author: Kathleen A. Neville
Author: Baba P. D. Inusa
Author: Yu Shyr
Author: Sharon Phillips
Author: Adetola A. Kassim
Author: Lori C. Jordan
Author: Muktar H. Aliyu
Author: Brittany V. Covert

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