Browsing by Author "Jayasinghe, V.L."

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    Efficacy and Safety of Oral Hydroxyurea in Patients with Transfusion Dependent β Thalassaemia: a Randomized Double-Blind Placebo-Controlled Clinical Trial
    (Sri Lanka Medical Association, 2020) Yasara, N.; Wickramarathne, N.; Silva, I.; Hameed, N.; Attanayaka, A.M.K.R.; Jayasinghe, V.L.; Wickramasinghe, N.; Rodrigo, R.; Perera, L.; Mettananda, K.C.D.; Manamperi, A.; Premawardhena, A.; Mettananda, S.
    INTRODUCTION AND OBJECTIVES: Patients with β- thalassaemia require blood transfusions and iron chelation for life. Hydroxyurea is a licenced medication for sickle cell disease but its usefulness in transfusion dependent 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 III randomized double-blind placebo-controlled clinical trial was conducted at Thalassaemia Unit of Colombo North Teaching Hospital in 2019. Forty-one patients with transfusion dependent β-thalassaemia were randomized into hydroxyurea (10-20mg/kg/day) or placebo (pharmaceutically inert capsule identical to hydroxyurea) groups. Transfused blood volume, pre-transfusion haemoglobin, haemoglobin F level and side effects were monitored monthly during 6- month treatment and 6-month follow-up periods. Adverse events were assessed by trained medical officers. The study was approved by ethics committee of University of Kelaniya and registered in Sri Lanka Clinical Trials Registry (SLCTR/ 2018/024). RESULTS: Of the 41 (hydroxyurea-20; placebo-21) patients, three discontinued treatment due to thrombocytopenia (hydroxyurea-2) and rash (placebo-1). Baseline characteristics of two groups were similar. Mean pre-transfusion haemoglobin (8.52+0.57 vs 8.38+0.55, p=0.45) and haemoglobin F levels (4.3+7.1% vs 3.1+1.9%, p=0.48) were higher in hydroxyurea group compared to placebo. Also, transfused blood volume was lower in hydroxyurea group (102+24ml/kg vs 111+27ml/kg, p=0.3). However, none were statistically significant. Based on elevation of haemoglobin F (>1.5% from baseline), we identified 6/18 patients as hydroxyurea responders. Hydroxyurea responders required significantly lower blood volume (87+13ml/kg) compared to non-responders (110+25ml/kg, p=0.05) and placebo group (111+27ml/kg, p<0.05) while maintaining higher pre-transfusion haemoglobin level (8.6+0.5 vs 8.4+0.5 and 8.3+0.5). No serious side effects were reported. CONCLUSIONS: One-third of patients with transfusion dependent β-thalassaemia responded to hydroxyurea treatment requiring 20% less blood compared to controls. No serious side effects were reported following hydroxyurea treatment.
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    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.