Academic Journal
Hydroxyurea for Children and Adults with Hemoglobin SC Disease.
| Τίτλος: | Hydroxyurea for Children and Adults with Hemoglobin SC Disease. |
|---|---|
| Συγγραφείς: | Dei-Adomakoh YA; Department of Haematology, University of Ghana Medical School, Accra, Ghana.; Department of Haematology, Korle Bu Teaching Hospital, Accra, Ghana., Segbefia CI; Department of Child Health, University of Ghana Medical School, Accra, Ghana.; Department of Child Health, Korle Bu Teaching Hospital, Accra, Ghana., Latham TS; Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati.; Global Health Center, Cincinnati Children's Hospital Medical Center, Cincinnati., Lane AC; Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati., Dzefi-Tettey K; Department of Radiology, Korle Bu Teaching Hospital, Accra, Ghana.; Department of Radiology, University of Health and Allied Sciences, Ho, Ghana., Amissah-Arthur K; Ophthalmology Unit, Department of Surgery, University of Ghana Medical School, Accra, Ghana.; Ophthalmology Unit, Department of Surgery, Korle Bu Teaching Hospital, Accra, Ghana., Corquaye O; Pharmacy Department, Korle Bu Teaching Hospital, Accra, Ghana., Korang L; Pharmacy Department, Korle Bu Teaching Hospital, Accra, Ghana., Mensah E; Department of Haematology, University of Ghana Medical School, Accra, Ghana., Ekpale P; Department of Haematology, University of Ghana Medical School, Accra, Ghana., Ghunney W; Department of Haematology, Korle Bu Teaching Hospital, Accra, Ghana., Tagoe LG; Department of Child Health, Korle Bu Teaching Hospital, Accra, Ghana., Oteng A; Department of Haematology, Korle Bu Teaching Hospital, Accra, Ghana., Amoako E; Department of Child Health, Korle Bu Teaching Hospital, Accra, Ghana., Schandorf E; Department of Child Health, Korle Bu Teaching Hospital, Accra, Ghana., Bankas E; Department of Haematology, Korle Bu Teaching Hospital, Accra, Ghana., Awuku NA; Department of Haematology, Korle Bu Teaching Hospital, Accra, Ghana., Seedah D; Department of Child Health, Korle Bu Teaching Hospital, Accra, Ghana., Stuber SE; Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati.; Global Health Center, Cincinnati Children's Hospital Medical Center, Cincinnati., Smart LR; Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati.; Global Health Center, Cincinnati Children's Hospital Medical Center, Cincinnati.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati., Ware RE; Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati.; Global Health Center, Cincinnati Children's Hospital Medical Center, Cincinnati.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati. |
| Πηγή: | NEJM evidence [NEJM Evid] 2025 Feb; Vol. 4 (2), pp. EVIDoa2400402. Date of Electronic Publication: 2024 Dec 08. |
| Τύπος έκδοσης: | Journal Article; Randomized Controlled Trial; Clinical Trial, Phase II; Equivalence Trial |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: NEJM Group, a division of the Massachusetts Medical Society Country of Publication: United States NLM ID: 9918317485806676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2766-5526 (Electronic) Linking ISSN: 27665526 NLM ISO Abbreviation: NEJM Evid Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Waltham, MA] : NEJM Group, a division of the Massachusetts Medical Society, [2022]- |
| Ιατρικοί όροι (MeSH): | Hydroxyurea*/therapeutic use , Hydroxyurea*/adverse effects , Antisickling Agents*/therapeutic use , Antisickling Agents*/adverse effects , Hemoglobin SC Disease*/drug therapy, Humans ; Female ; Male ; Child ; Adult ; Double-Blind Method ; Adolescent ; Young Adult ; Child, Preschool ; Ghana ; Prospective Studies ; Quality of Life ; Middle Aged ; Treatment Outcome ; Acute Chest Syndrome |
| Περίληψη: | Background: Hemoglobin SC (HbSC) is a common sickle hemoglobinopathy that causes acute complications, chronic organ damage, and early death with no established disease-modifying treatment. In this trial, we examined the safety and efficacy of hydroxyurea treatment in patients with HbSC. Methods: Prospective Identification of Variables as Outcomes for Treatment (PIVOT) was a double-blind, randomized, placebo-controlled, non-inferiority phase 2 trial in which we assigned children and adults with HbSC in Ghana to 12 months of hydroxyurea or placebo. The primary end point was hematologic dose-limiting toxicities (DLTs), including cytopenias or elevated hemoglobin levels during 12 months of blinded treatment. Clinical end points included vaso-occlusive pain events, acute chest syndrome, hospitalizations, transfusions, and malaria. Quality-of-life measures, organ function assessments, and rheological measurements were also collected. Results: Of the 243 enrolled patients (118 female), 212 eligible participants initiated blinded treatment at 20.0±5.0 mg/kg/day. DLTs occurred in more participants on hydroxyurea (33%) than the placebo (11%), with a difference of 22 percentage points (95% confidence interval [CI],11 to 34 percentage points), which exceeded the predefined 15 percentage point noninferiority margin. Elevated levels of hemoglobin occurred in 12 participants on hydroxyurea and 10 on the placebo. Hydroxyurea treatment was associated with 57.0 versus 149.6 vaso-occlusive pain events per 100 person-years (incidence rate ratio [IRR] 0.38; 95% CI, 0.28 to 0.52), and 12.9 versus 30.6 hospitalizations per 100 person-years (IRR 0.42; 95% CI, 0.22 to 0.81). A composite of acute sickle-related events occurred in 37 participants on hydroxyurea versus 69 participants on placebo (IRR 0.39; (95% CI, 0.26 to 0.59), a difference observed in both children and adults. Conclusions: The PIVOT trial did not meet its primary end point. Hydroxyurea at 20 mg/kg in patients with HbSC was associated with more hematologic DLTs than placebo, but most were mild and transient. Hydroxyurea was associated with less vaso-occlusive pain and fewer sickle-related events in both children and adults; a new trial will need to be done to establish the efficacy of this approach. (Funded by Theravia; Pan-African Clinical Trials Registry number, PACTR 202108893981080). |
| Σχόλια: | Comment in: NEJM Evid. 2025 Feb;4(2):EVIDe2400449. doi: 10.1056/EVIDe2400449.. (PMID: 39873545) |
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| Grant Information: | K23 HL153763 United States HL NHLBI NIH HHS |
| Substance Nomenclature: | X6Q56QN5QC (Hydroxyurea) 0 (Antisickling Agents) |
| Entry Date(s): | Date Created: 20241208 Date Completed: 20250128 Latest Revision: 20260202 |
| Update Code: | 20260202 |
| PubMed Central ID: | PMC12577646 |
| DOI: | 10.1056/EVIDoa2400402 |
| PMID: | 39647172 |
| Βάση Δεδομένων: | MEDLINE |
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