A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia
Abstract Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in β-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in trans...
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| Format: | Article |
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Nature Portfolio
2022-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-06774-8 |
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| author | Nirmani Yasara Nethmi Wickramarathne Chamila Mettananda Ishari Silva Nizri Hameed Kumari Attanayaka Rexan Rodrigo Nirmani Wickramasinghe Lakshman Perera Aresha Manamperi Anuja Premawardhena Sachith Mettananda |
| author_facet | Nirmani Yasara Nethmi Wickramarathne Chamila Mettananda Ishari Silva Nizri Hameed Kumari Attanayaka Rexan Rodrigo Nirmani Wickramasinghe Lakshman Perera Aresha Manamperi Anuja Premawardhena Sachith Mettananda |
| author_sort | Nirmani Yasara |
| collection | DOAJ |
| description | Abstract Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in β-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in transfusion-dependent β-thalassaemia. Sixty patients were assigned 1:1 to oral hydroxyurea 10–20 mg/kg/day or placebo for 6 months by stratified block randomisation. Hydroxyurea treatment did not alter the blood transfusion volume overall. However, a significantly higher proportion of patients on hydroxyurea showed increases in fetal haemoglobin percentage (89% vs. 59%; p < 0.05) and reductions in erythropoietic stress as measured by soluble transferrin receptor concentration (79% vs. 40%; p < 0.05). Based on fetal haemoglobin induction (> 1.5%), 44% of patients were identified as hydroxyurea-responders. Hydroxyurea-responders, required significantly lower blood volume (77 ± SD27ml/kg) compared to hydroxyurea-non-responders (108 ± SD24ml/kg; p < 0.01) and placebo-receivers (102 ± 28ml/kg; p < 0.05). Response to hydroxyurea was significantly higher in patients with HbE β-thalassaemia genotype (50% vs. 0%; p < 0.01) and Xmn1 polymorphism of the γ-globin gene (67% vs. 27%; p < 0.05). We conclude that oral hydroxyurea increased fetal haemoglobin percentage and reduced erythropoietic stress of ineffective erythropoiesis in patients with transfusion-dependent β-thalassaemia. Hydroxyurea reduced the transfusion burden in approximately 40% of patients. Response to hydroxyurea was higher in patients with HbE β-thalassaemia genotype and Xmn1 polymorphism of the γ-globin gene. |
| first_indexed | 2024-12-23T23:54:39Z |
| format | Article |
| id | doaj.art-4cc1a47132c94b1ba3eb73830eb877e0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-23T23:54:39Z |
| publishDate | 2022-02-01 |
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| spelling | doaj.art-4cc1a47132c94b1ba3eb73830eb877e02022-12-21T17:25:16ZengNature PortfolioScientific Reports2045-23222022-02-0112111110.1038/s41598-022-06774-8A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemiaNirmani Yasara0Nethmi Wickramarathne1Chamila Mettananda2Ishari Silva3Nizri Hameed4Kumari Attanayaka5Rexan Rodrigo6Nirmani Wickramasinghe7Lakshman Perera8Aresha Manamperi9Anuja Premawardhena10Sachith Mettananda11Department of Paediatrics, Faculty of Medicine, University of KelaniyaDepartment of Paediatrics, Faculty of Medicine, University of KelaniyaDepartment of Pharmacology, Faculty of Medicine, University of KelaniyaAdult and Adolescent Thalassaemia Centre, Colombo North Teaching HospitalAdult and Adolescent Thalassaemia Centre, Colombo North Teaching HospitalAdult and Adolescent Thalassaemia Centre, Colombo North Teaching HospitalAdult and Adolescent Thalassaemia Centre, Colombo North Teaching HospitalAdult and Adolescent Thalassaemia Centre, Colombo North Teaching HospitalAdult and Adolescent Thalassaemia Centre, Colombo North Teaching HospitalMolecular Medicine Unit, Faculty of Medicine, University of KelaniyaAdult and Adolescent Thalassaemia Centre, Colombo North Teaching HospitalDepartment of Paediatrics, Faculty of Medicine, University of KelaniyaAbstract Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in β-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in transfusion-dependent β-thalassaemia. Sixty patients were assigned 1:1 to oral hydroxyurea 10–20 mg/kg/day or placebo for 6 months by stratified block randomisation. Hydroxyurea treatment did not alter the blood transfusion volume overall. However, a significantly higher proportion of patients on hydroxyurea showed increases in fetal haemoglobin percentage (89% vs. 59%; p < 0.05) and reductions in erythropoietic stress as measured by soluble transferrin receptor concentration (79% vs. 40%; p < 0.05). Based on fetal haemoglobin induction (> 1.5%), 44% of patients were identified as hydroxyurea-responders. Hydroxyurea-responders, required significantly lower blood volume (77 ± SD27ml/kg) compared to hydroxyurea-non-responders (108 ± SD24ml/kg; p < 0.01) and placebo-receivers (102 ± 28ml/kg; p < 0.05). Response to hydroxyurea was significantly higher in patients with HbE β-thalassaemia genotype (50% vs. 0%; p < 0.01) and Xmn1 polymorphism of the γ-globin gene (67% vs. 27%; p < 0.05). We conclude that oral hydroxyurea increased fetal haemoglobin percentage and reduced erythropoietic stress of ineffective erythropoiesis in patients with transfusion-dependent β-thalassaemia. Hydroxyurea reduced the transfusion burden in approximately 40% of patients. Response to hydroxyurea was higher in patients with HbE β-thalassaemia genotype and Xmn1 polymorphism of the γ-globin gene.https://doi.org/10.1038/s41598-022-06774-8 |
| spellingShingle | Nirmani Yasara Nethmi Wickramarathne Chamila Mettananda Ishari Silva Nizri Hameed Kumari Attanayaka Rexan Rodrigo Nirmani Wickramasinghe Lakshman Perera Aresha Manamperi Anuja Premawardhena Sachith Mettananda A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia Scientific Reports |
| title | A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia |
| title_full | A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia |
| title_fullStr | A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia |
| title_full_unstemmed | A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia |
| title_short | A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia |
| title_sort | randomised double blind placebo controlled clinical trial of oral hydroxyurea for transfusion dependent β thalassaemia |
| url | https://doi.org/10.1038/s41598-022-06774-8 |
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