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Publications

Clinical Trial, Phase II Journal Article Ppublish 7 citations

PubMed: 35977532 DOI: 10.1159/000526322

Stroke Prevention with Hydroxyurea Enabled through Research and Education: A Phase 2 Primary Stroke Prevention Trial in Sub-Saharan Africa.

Acta Haematol 146(2):95-105

Authors: Luke R Smart, Emmanuela E Ambrose, Georgina Balyorugulu, Primrose Songoro, Idd Shabani, Protas Komba, Mwesige Charles, Thad A Howard, Kathryn E McElhinney, Sara M O'Hara, Jodie Odame, Maria Nakafeero, Janet Adams, Susan E Stuber, Adam Lane, Teresa S Latham, Abel N Makubi, Russell E Ware

Affiliations

  • Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
  • Global Health Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
  • Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
  • Catholic University of Health & Allied Sciences, Mwanza, Tanzania.
  • Bugando Medical Centre, Mwanza, Tanzania.
  • Catholic University of Health & Allied Sciences, Mwanza, Tanzania. Bugando Medical Centre, Mwanza, Tanzania.
  • Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
  • Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
  • Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Global Health Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Abstract

INTRODUCTION

Stroke is a severe complication of sickle cell anemia (SCA), with devastating sequelae. Transcranial Doppler (TCD) ultrasonography predicts stroke risk, but implementing TCD screening with suitable treatment for primary stroke prevention in low-resource environments remains challenging. SPHERE (NCT03948867) is a prospective phase 2 open-label hydroxyurea trial for SCA in Tanzania.

METHODS

After formal training and certification, local personnel screened children 2-16 years old; those with conditional (170-199 cm/s) or abnormal (≥200 cm/s) time-averaged mean velocities (TAMVs) received hydroxyurea at 20 mg/kg/day with dose escalation to maximum tolerated dose (MTD). The primary study endpoint is change in TAMV after 12 months of hydroxyurea; secondary endpoints include SCA-related clinical events, splenic volume and function, renal function, infections, hydroxyurea pharmacokinetics, and genetic modifiers.

RESULTS

Between April 2019 and April 2020, 202 children (average 6.8 ± 3.5 years, 53% female) enrolled and underwent TCD screening; 196 were deemed eligible by DNA testing. Most had numerous previous hospitalizations and transfusions, with low baseline hemoglobin (7.7 ± 1.1 g/dL) and %HbF (9.3 ± 5.4%). Palpable splenomegaly was present at enrollment in 49 (25%); average sonographic splenic volume was 103 mL (range 8-1,045 mL). TCD screening identified 22% conditional and 2% abnormal velocities, with hydroxyurea treatment initiated in 96% (45/47) eligible children.

CONCLUSION

SPHERE has built local capacity with high-quality research infrastructure and TCD screening for SCA in Tanzania. Fully enrolled participants have a high prevalence of elevated baseline TCD velocities and splenomegaly. SPHERE will prospectively determine the benefits of hydroxyurea at MTD for primary stroke prevention, anticipating expanded access to hydroxyurea treatment across Tanzania.

MeSH

Splenomegaly, Hematology, Stroke, Research, Therapeutics, Education, Child, Hydroxyurea

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