Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent β-thalassaemia(Nature Publishing Group, 2022) Yasara, N.; Wickramarathne, N.; Mettananda, C.; Silva, I.; Hameed, N.; Attanayaka, K.; Rodrigo, R.; Wickramasinghe, N.; Perera, L.; Manamperi, A.; Premawardhena, A.; Mettananda, S.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.Item Hydroxyurea for transfusion dependent β-thalassaemia: A randomized double-blind placebo-controlled clinical trial(Sri Lanka Medical Association, 2021) Yasara, N.; Wickramarathne, N.; Silva, I.; Hameed, N.; Attanayaka, A.M.K.R.; Jayasinghe, V.L.; Gunathilaka, P.A.C.K.; Wickramasinghe, N.; Rodrigo, R.; Perera, L; Perera, P.S.; Mettananda, K.C.D.; Manamperi, A.; Premawardhena, A.; Mettananda, S.Introduction and objectives Hydroxyurea induces fetal haemoglobin in vitro however, its clinical usefulness in β-thalassaemia is unclear. Here, we aim to assess the efficacy and safety of oral hydroxyurea in patients with transfusion dependent β-thalassaemia. Methods A phase 3 randomized double-blind placebo-controlled clinical trial was conducted at Colombo North Teaching Hospital in 2019/20. Sixty patients with transfusion dependent β-thalassaemia were randomized into hydroxyurea (10-20mg/kg/day) or placebo groups. Transfused blood volume, pre-transfusion haemoglobin, fetal haemoglobin and adverse effects were monitored during 6-month treatment and post-treatment periods. The study was approved by the ethics committee of University of Kelaniya and registered in Sri Lanka Clinical Trials Registry (SLCTR/2018/024). Results Fifty-four (hydroxyurea-27; placebo-27) patients completed the trial. Mean pre-transfusion haemoglobin (8.2±0.8g/ dLvs8.0±0.88g/dL, p=0.43) and fetal haemoglobin levels (7.9±11.2%vs4.6±4.3%, p=0.17) were higher in hydroxyurea group compared to placebo. Also, transfused blood volume was lower in the hydroxyurea group (94±29ml/kgvs102±28ml/kg, p=0.34). However, none were statistically significant. Based on elevation of fetal haemoglobin (>1.5% from baseline), we identified 12/27 patients who respond well to hydroxyurea (hydroxyurea-responders). Hydroxyurea-responders required significantly lower blood volume (77±27ml/kg) compared to non-responders (108±24ml/kg, p<0.01) and placebo group (102±28ml/kg, p<0.05). HbE β-thalassaemia sub-type (p<0.01) and Xmn1 polymorphism of γ-globin gene (p<0.05) were significant predictors of response to hydroxyurea. No serious side effects due to hydroxyurea were reported. Conclusion Over 40% of patients with transfusion dependent β-thalassaemia- specifically those with HbE β-thalassaemia and Xmn1 polymorphism of γ-globin gene- responded to hydroxyurea and required 25% less blood compared to controls. No serious adverse effects were reported following hydroxyurea treatment.