Evaluation of the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2): a multicentre, randomised, open-label, non-inferiority, phase 3 trial

Maggio, Aurelio; Kattamis, Antonis; Felisi, Mariagrazia; Reggiardo, Giorgio; El‐Beshlawy, Amal; Béjaoui, Mohamed; Sherief, Laila M.; Christou, Soteroula; Cosmi, Carlo; Pasqua, Oscar Della; Vecchio, Giovanni Carlo Del; Filosa, Aldo; Cuccia, Liana; Hassab, Hoda; Kreka, Manika; Origa, Raffaella; Putti, Maria Caterina; Spino, Michael; Telfer, Paul; Tempesta, Bianca; Vitrano, Angela; Tsang, Yu Chung; Zaka, Ariana; Tricta, Fernando; Bonifazi, Donato; Ceci, Adriana

doi:10.1016/s2352-3026(20)30100-9

Cited by 55 publications

(55 citation statements)

References 17 publications

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“…A study showed that the patients who were receiving DFX reported 90% compliance, whereas those receiving DFO reported 40% [6]. Additionally, a study reported similar and high compliance rates between DFP (95%) and DFX (97%) in pediatric patients with transfusion-dependent hemoglobinopathies [7]. This survey disclosed 77.4% of the patients reported more than 80% compliance with DFX, which is low in comparison to the published reports.…”

Section: Discussionmentioning

confidence: 66%

Comparison of Compliance of Different Iron Chelators Including Original and Bioequivalents of Deferasirox

Aksu¹,

Özbek

Söker

et al. 2020

Acta Medica

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Objective: The current iron chelation therapy regimens include deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX) in transfusion-dependent patients. Compliance with iron-chelating therapy is one of the significant determinants of mortality and morbidities related to iron loading in chronically transfused patients. This survey aims to compare the compliance and the satisfaction of DFO, DFP, and DFX formulations in patients who have iron-overloading in three hematology centers from Turkey. Moreover, bioequivalent (generic) formulations of dispersible DFX tablet compared with the original formulation in terms of taste and treatment compliance. Patients and Methods: A written questionnaire with a list of pre-set questions was applied to measure patient-reported outcomes to a total of 85 patients, where 77 had beta-thalassemia major, 7 had beta-thalassemia intermedia, and 1 had sickle cell anemia diagnoses. Results: The patients’ median age at enrollment was 15 years (range 7 – 42). The compliance was below 50% in 8 (18.6%), 4 (16%), and 5 (6.7%) in patients receiving DFO, DFP, and DFX, respectively. Additionally the compliance was below 80% in 16 (37.2%), 9 (36%), and 17 (22.6%) in patients receiving DFO, DFP, and DFX, respectively. It was found that 39 (47%) patients had compliance problems due to the dispersible DFX tablet formulations’ taste, except combination therapies. There was no difference between the currently used oral chelators in terms of taste and treatment compliance. Conclusion: This study draws attention to compliance problems in patients with iron-loading anemias, partly due to the unpleasant taste of DFX. Improving patient satisfaction and compliance with iron-chelator therapy may reduce complications of iron overload.

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Section: Discussionmentioning

confidence: 66%

Comparison of Compliance of Different Iron Chelators Including Original and Bioequivalents of Deferasirox

Aksu¹,

Özbek

Söker

et al. 2020

Acta Medica

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“…DEEP-2 study represents a unique GCP-compliant active-controlled multi-national paediatric trial involving EU and non-EU countries [24] in which ad hoc measures were in place to overcome the regulatory and ethical differences among countries and sites, often delaying or preventing the starting of such a trial.…”

Section: Discussionmentioning

confidence: 99%

Ethical and procedural issues for applying researcher-driven multi-national paediatric clinical trials in and outside the European Union: the challenging experience of the DEEP project

et al. 2021

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Background We describe our experience from a multi-national application of a European Union-funded research-driven paediatric trial (DEEP-2, EudraCT 2012-000353-31; NCT01825512). This paper aims to evaluate the impact of the local and national rules on the trial authorisation process in European and non-European countries. National/local provisions and procedures, number of Ethics Committees and Competent Authorities to be addressed, documentation required, special provisions for the paediatric population, timelines for completing the authorisation process and queries received were collected; compliance with the European provisions were evaluated. Descriptive analysis, Wilcoxon Rank-Sum test and General Linear Model analysis were used to determine factors potentially influencing the timelines. The Cluster Analysis procedure was used to identify homogenous groups of cases. Result The authorisation process was completed in 7.7 to 53.8 months in European countries and in 17.1 to 27.1 months in non-European countries. The main factors influencing these timelines were the requests for changes/clarifications in European countries and the different national legislations in non-European countries. Conclusion This work confirms that the procedures and requirements for the clinical trial application of a paediatric trial are different. In the European Union, the timeframes for submission were generally harmonised but longer. In non-European countries, delays were caused by national dispositions but the entire authorisation process resulted faster with less requests from ECs/CAs. The upcoming application of Regulation (EU) 536/2014 is expected to harmonise practices in Europe and possibly outside. Networks on paediatric research acting at international level will be crucial in this effort.

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“…102 There are currently three iron chelators licensed and approved for use in Europe and the USA, all of which have been shown to be effective in mitigating iron overload in patients with hemoglobinopathies (Table 3). [102][103][104] Successful chelation therapy is dependent upon the patients' adherence and the tolerability and toxicities of the drugs used.…”

Section: Iron Overloadmentioning

confidence: 99%

Red cell transfusion and alloimmunization in sickle cell disease

Linder

Chou

2021

haematol

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Red cell transfusion remains a critical component of care for acute and chronic complications of sickle cell disease. Randomized clinical trials demonstrated the benefits of transfusion therapy for prevention of primary and secondary strokes and postoperative acute chest syndrome. Transfusion for splenic sequestration, acute chest syndrome, and acute stroke are guided by expert consensus recommendations. Despite overall improvements in blood inventory safety, adverse effects of transfusion are prevalent among patients with sickle cell disease and include alloimmunization, acute and delayed hemolytic transfusion reactions, and iron overload. Judicious use of red cell transfusions, optimization of red cell antigen matching, and the use of erythrocytapheresis and iron chelation can minimize adverse effects. Early recognition and management of hemolytic transfusion reactions can avert poor clinical outcomes. In this review, we discuss transfusion methods, indications, and complications in sickle cell disease with an emphasis on alloimmunization.

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Evaluation of the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2): a multicentre, randomised, open-label, non-inferiority, phase 3 trial

Cited by 55 publications

References 17 publications

Comparison of Compliance of Different Iron Chelators Including Original and Bioequivalents of Deferasirox

Comparison of Compliance of Different Iron Chelators Including Original and Bioequivalents of Deferasirox

Ethical and procedural issues for applying researcher-driven multi-national paediatric clinical trials in and outside the European Union: the challenging experience of the DEEP project

Red cell transfusion and alloimmunization in sickle cell disease

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