{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:29:43Z","timestamp":1793316583225,"version":"4.5.0"},"reference-count":26,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"unspecified","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,1,26]]},"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Despite the improvement in medical management, many patients with transfusion-dependent \u03b2-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent \u03b2-thalassaemia with very high iron overload.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent \u03b2-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6\u2009months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6\u2009months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P\/06\/02\/2023). The trial results will be disseminated in scientific publications in reputed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR\/2023\/010).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-077342","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T21:40:49Z","timestamp":1707428449000},"page":"e077342","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent \u03b2-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial"],"prefix":"10.1136","volume":"14","author":[{"given":"Anuja","family":"Premawardhena","sequence":"first","affiliation":[{"name":"Colombo North Teaching Hospital, Ragama, Sri Lanka"},{"name":"Department of Medicine, University of Kelaniya, Kelaniya, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chamodi","family":"Perera","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Kelaniya, Kelaniya, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muditha Nayana","family":"Wijethilaka","sequence":"additional","affiliation":[{"name":"Colombo North Teaching Hospital, Ragama, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakuni Keshani","family":"Wanasinghe","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Kelaniya, Kelaniya, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R H M G","family":"Rajakaruna","sequence":"additional","affiliation":[{"name":"Lady Ridgeway Hospital for Children, Colombo, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A N K K","family":"Samarasinghe","sequence":"additional","affiliation":[{"name":"Lady Ridgeway Hospital for Children, Colombo, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senani","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Kelaniya, Kelaniya, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0760-0418","authenticated-orcid":false,"given":"Sachith","family":"Mettananda","sequence":"additional","affiliation":[{"name":"Colombo North Teaching Hospital, Ragama, Sri Lanka"},{"name":"Department of Paediatrics, University of Kelaniya, Kelaniya, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"2025121401365743000_14.2.e077342.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31822-6"},{"key":"2025121401365743000_14.2.e077342.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60283-3"},{"key":"2025121401365743000_14.2.e077342.3","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.blre.2018.02.001","article-title":"A paradigm shift on beta-thalassaemia treatment: How will we manage this old disease with new therapies?","volume":"32","author":"Cappellini","year":"2018","journal-title":"Blood Rev"},{"key":"2025121401365743000_14.2.e077342.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2021838"},{"key":"2025121401365743000_14.2.e077342.5","doi-asserted-by":"crossref","first-page":"e134","DOI":"10.1016\/S2214-109X(21)00446-0","article-title":"Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study","volume":"10","author":"Premawardhena","year":"2022","journal-title":"Lancet Glob Health"},{"key":"2025121401365743000_14.2.e077342.6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/ejh.13410","article-title":"The changing epidemiology of the ageing thalassaemia populations: A position statement of the Thalassaemia International Federation","volume":"105","author":"Farmakis","year":"2020","journal-title":"Eur J Haematol"},{"key":"2025121401365743000_14.2.e077342.7","doi-asserted-by":"crossref","DOI":"10.1097\/HS9.0000000000000732","article-title":"2021 Thalassaemia International Federation Guidelines for the Management of Transfusion-dependent Thalassemia","volume":"6","author":"Farmakis","year":"2021","journal-title":"Hemasphere"},{"key":"2025121401365743000_14.2.e077342.8","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1056\/NEJMra1800219","article-title":"The Role of Deferiprone in Iron Chelation","volume":"379","author":"Hider","year":"2018","journal-title":"N Engl J Med"},{"key":"2025121401365743000_14.2.e077342.9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-06-818187"},{"key":"2025121401365743000_14.2.e077342.10","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.freeradbiomed.2021.02.028","article-title":"Oxidative status in the \u03b2-thalassemia syndromes in Sri Lanka; a cross-sectional survey","volume":"166","author":"Allen","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"2025121401365743000_14.2.e077342.11","doi-asserted-by":"crossref","unstructured":"Mettananda S , Pathiraja H , Peiris R , et al . Blood transfusion therapy for \u03b2\u2010thalassemia major and hemoglobin E \u03b2\u2010thalassemia: Adequacy, trends, and determinants in Sri Lanka. Pediatric Blood & Cancer 2019;66. doi:10.1002\/pbc.27643 Available: https:\/\/onlinelibrary.wiley.com\/toc\/15455017\/66\/5","DOI":"10.1002\/pbc.27643"},{"key":"2025121401365743000_14.2.e077342.12","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/ped.14444","article-title":"Using of deferasirox and deferoxamine in refractory iron overload thalassemia","volume":"63","author":"Takpradit","year":"2021","journal-title":"Pediatr Int"},{"key":"2025121401365743000_14.2.e077342.13","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0220852","article-title":"A nationwide survey of hospital-based thalassemia patients and standards of care and A preliminary assessment of the national prevention program in Sri Lanka","volume":"14","author":"Premawardhana","year":"2019","journal-title":"PLoS One"},{"key":"2025121401365743000_14.2.e077342.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2017.11.003"},{"key":"2025121401365743000_14.2.e077342.15","doi-asserted-by":"crossref","DOI":"10.3389\/fgeed.2021.752278","article-title":"Genetic and Epigenetic Therapies for \u03b2-Thalassaemia by Altering the Expression of \u03b1-Globin Gene","volume":"3","author":"Mettananda","year":"2021","journal-title":"Front Genome Ed"},{"key":"2025121401365743000_14.2.e077342.16","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/bmt.2015.293","article-title":"Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000-2010","volume":"51","author":"Baronciani","year":"2016","journal-title":"Bone Marrow Transplant"},{"key":"2025121401365743000_14.2.e077342.17","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1056\/NEJMoa1910182","article-title":"A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent \u03b2-Thalassemia","volume":"382","author":"Cappellini","year":"2020","journal-title":"N Engl J Med"},{"key":"2025121401365743000_14.2.e077342.18","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-06774-8","article-title":"A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent \u03b2-thalassaemia","volume":"12","author":"Yasara","year":"2022","journal-title":"Sci Rep"},{"key":"2025121401365743000_14.2.e077342.19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1705342"},{"key":"2025121401365743000_14.2.e077342.20","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2031054"},{"key":"2025121401365743000_14.2.e077342.21","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-00479-7","article-title":"Editing an \u03b1-globin enhancer in primary human hematopoietic stem cells as a treatment for \u03b2-thalassemia","volume":"8","author":"Mettananda","year":"2017","journal-title":"Nat Commun"},{"key":"2025121401365743000_14.2.e077342.22","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-37604-8","article-title":"Direct correction of haemoglobin E \u03b2-thalassaemia using base editors","volume":"14","author":"Badat","year":"2023","journal-title":"Nat Commun"},{"key":"2025121401365743000_14.2.e077342.23","article-title":"Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia","volume":"5","author":"Fortin","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"2025121401365743000_14.2.e077342.24","doi-asserted-by":"crossref","DOI":"10.4084\/mjhid.2018.066","article-title":"Deferasirox: Over a Decade of Experience in Thalassemia","volume":"10","author":"Moukalled","year":"2018","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"2025121401365743000_14.2.e077342.25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/tme.12188","article-title":"Combination therapy - deferasirox and deferoxamine - in thalassemia major patients in emerging countries with limited resources","volume":"25","author":"Arandi","year":"2015","journal-title":"Transfus Med"},{"key":"2025121401365743000_14.2.e077342.26","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/bjh.14776","article-title":"Serum ferritin in the diagnosis of cardiac and liver iron overload in thalassaemia patients real-world practice: a multicentre study","volume":"182","author":"Krittayaphong","year":"2018","journal-title":"Br J Haematol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-077342","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T09:37:06Z","timestamp":1765705026000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-077342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,8]]},"published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1136\/bmjopen-2023-077342"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-077342","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2]]}}}