{"doi":"10.1002/ajh.25900","title":"Moderate fixed‐dose hydroxyurea for primary prevention of strokes in Nigerian children with sickle cell disease: Final results of the <scp>SPIN</scp> trial","abstract":"To the Editor: In children with sickle cell anemia (SCA) living in high-income settings, the routine use of transcranial Doppler (TCD) measurements, coupled with monthly blood transfusion therapy for children with abnormal velocities (≥200 cm/s, non-imaging), resulted in a 92% relative risk reduction in strokes when compared to no treatment.1 More recently, the TWITCH Trial demonstrated that children with abnormal TCD measurements and no evidence of magnetic resonance angiography-defined cerebral vasculopathy, after 1 year of initial regular blood transfusion therapy, could be transitioned to hydroxyurea therapy at the maximum tolerated dose.2 However, initial regular blood transfusion therapy for primary stroke prevention is not feasible for the vast majority of the children with SCA living in low- and middle-income settings.3 Furthermore, limited data are available to determine whether initial treatment with hydroxyurea rather than blood transfusion therapy is a durable therapy for primary stroke prevention. To address this gap in knowledge for preventing strokes in children with SCA living in Africa, we tested the hypothesis that moderate fixed-dose hydroxyurea (~20 mg/kg/d) for primary stroke prevention was feasible in a low-income setting (Kano, Nigeria). We previously demonstrated in the Stroke Prevention in Nigeria (SPIN) Trial (NCT01801423) that hydroxyurea was acceptable and safe for children with SCA and abnormal TCD measurements.4 We have extended the feasibility trial for approximately 5 years to test the hypotheses that moderate fixed-dose hydroxyurea will: (a) not result in an excess incidence rate of serious adverse events (death or stroke) when compared to a group of children with SCA and TCD measurements <200 cm/s not receiving hydroxyurea; (b) be comparable to the stroke incidence rate in children with abnormal TCD measurements in the STOP Trial that were initially and only treated with regular blood transfusion therapy.1 We report the final results of the SPIN Trial. At trial entry, eligible participants were screened with the TCD non-imaging technique to determine increased stroke risk, defined as two independent measurements of time-averaged mean maximum velocity (TAMMV) of ≥200 cm/s or one measurement of ≥220 cm/s in the middle cerebral artery (MCA). Families of children with abnormal TCDs were offered regular blood transfusion therapy as standard care. If families refused regular blood transfusion, moderate fixed-dose hydroxyurea (~20 mg/kg/d) was offered via the SPIN trial; children were evaluated monthly with surveillance complete blood counts (CBCs). To primarily address whether hydroxyurea was associated with an increased incidence of death when compared to children with SCA in the same age group not treated with hydroxyurea, we included a comparison group of children with SCA who were screened and had a TCD measurement of <200 cm/s and who agreed to be followed as part of routine care. Malaria prophylaxis and penicillin prophylaxis were prescribed to all participants as standard care. Serious adverse events including death or stroke in the treatment and comparison groups, based on the World Health Organization criteria,5 were recorded and compared. Twenty-nine children with abnormal TCD measurements were identified and treated with moderate fixed-dose hydroxyurea for primary stroke prevention, and 206 children were included in the comparison group. No caregiver of a child with abnormal TCD measurements elected to have their child treated with regular blood transfusion therapy. Among the comparison group, standard care TCD screening was performed on average every 12 months. Four children developed abnormal TCD measurements and crossed over to the treatment group. Baseline features and clinical outcomes of the treatment and comparison groups are shown in Table 1. The median time on hydroxyurea therapy (follow-up time) was 4.8 years (IQR: 3.7-5.6). The stroke incidence rate among participants on hydrox","journal":"American Journal of Hematology","year":2020,"id":66620,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353136,"name":"Shehu U. Abdullahi","orcid":"0000-0001-5567-9629","position":1,"is_corresponding":false},{"id":354684,"name":"Shehi Ali Abubakar","orcid":null,"position":2,"is_corresponding":false},{"id":309669,"name":"Binta W. Jibir","orcid":null,"position":3,"is_corresponding":false},{"id":354685,"name":"Hauwa Aminu","orcid":null,"position":4,"is_corresponding":false},{"id":354686,"name":"Aliyu Tijjani","orcid":null,"position":5,"is_corresponding":false},{"id":353137,"name":"Muhammad Aliyu Abba","orcid":"0000-0002-7944-1866","position":6,"is_corresponding":false},{"id":354687,"name":"Musa A. Tabari","orcid":null,"position":7,"is_corresponding":false},{"id":354688,"name":"Aisha A. Galadanci","orcid":null,"position":8,"is_corresponding":false},{"id":354689,"name":"Awwal Musa Borodo","orcid":null,"position":9,"is_corresponding":false},{"id":354690,"name":"Raymond Belonwu","orcid":null,"position":10,"is_corresponding":false},{"id":353138,"name":"Auwal Salihu","orcid":"0000-0002-8232-9744","position":11,"is_corresponding":false},{"id":353139,"name":"Mark Rodeghier","orcid":"0000-0001-7258-0073","position":12,"is_corresponding":false},{"id":353140,"name":"Djamila L. Ghafuri","orcid":"0000-0002-8227-0834","position":13,"is_corresponding":false},{"id":354691,"name":"Brittany V. Covert Greene","orcid":null,"position":14,"is_corresponding":false},{"id":52773,"name":"Kathleen Neville","orcid":null,"position":15,"is_corresponding":false},{"id":353141,"name":"Adetola A. Kassim","orcid":"0000-0002-0484-5903","position":16,"is_corresponding":false},{"id":353142,"name":"Fenella J. Kirkham","orcid":"0000-0002-2443-7958","position":17,"is_corresponding":false},{"id":292916,"name":"Lori C. Jordan","orcid":"0000-0001-7240-0415","position":18,"is_corresponding":false},{"id":353143,"name":"Muktar H. Aliyu","orcid":"0000-0001-9504-4679","position":19,"is_corresponding":false},{"id":24956,"name":"Michael R. DeBaun","orcid":"0000-0002-0574-1604","position":20,"is_corresponding":false},{"id":353135,"name":"Najibah A. Galadanci","orcid":"0000-0002-6853-5023","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-18T21:14:50.590588Z","pmid":"32510680","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}