Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis:
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ORIGINAL ARTICLE
Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments Aurélia Bertholet-Thomas 1 & Catherine Guittet 2 & Maria A. Manso-Silván 2 & Arnaud Castang 2 & Véronique Baudouin 3 & Mathilde Cailliez 4 & Massimo Di Maio 5 & Olivia Gillion-Boyer 6 & Emilija Golubovic 7 & Jérôme Harambat 8 & Alexandre Klein 9 & Bertrand Knebelmann 10 & François Nobili 11 & Robert Novo 12 & Ludmila Podracka 13 & Gwenaëlle Roussey-Kesler 14 & Christos Stylianou 15 & Luc-André Granier 2 Received: 12 March 2020 / Revised: 16 June 2020 / Accepted: 25 June 2020 # The Author(s) 2020
Abstract Background Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release formulation, ADV7103, has been developed to achieve a sustained effect with an improved dosing scheme. Methods In a multicenter, open-label, non-inferiority trial (n = 37), patients with dRTA were switched from SoC to ADV7103. Mean plasma bicarbonate values and proportion of responders during steady state therapy with both treatments were compared, as were other blood and urine parameters, as well as acceptability, tolerability, and safety. Results When switching from SoC to ADV7103, the number of daily intakes was reduced from a median of three to twice daily. Mean plasma bicarbonate was increased and non-inferiority of ADV7103 was demonstrated (p < 0.0001, per protocol), as was statistical superiority (p = 0.0008, intention to treat [ITT]), and the response rate increased from 43 to 90% with ADV7103 (p < 0.001, ITT). Urine calcium/citrate ratio was reduced below the threshold for risk of lithogenesis with ADV7103 in 56% of previously non-responders with SoC (p = 0.021, ITT). Palatability was improved (difference [95% CI] of 25 [10.7, 39.2] mm) Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00467-020-04693-2) contains supplementary material, which is available to authorized users. * Aurélia Bertholet-Thomas [email protected] 1
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Centre de Référence des Maladies Rénales Rares – Néphrogones – Hôpital Femme Mère Enfant – Filière ORKiD, Hospices Civils de Lyon, Bron, France Advicenne, Nîmes, France
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Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, France
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Service de Pédiatrie Multidisciplinaire, Hôpital de la Timone, AP-HM, Marseille, France
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Service de Réanimation Néonatale et Néonatologie, CHU de Nîmes, Nîmes, France
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Service de Néphrologie Pédiatrique, Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte (MARHEA), Institut Imagine, Hôpital Necker-Enfants Malades, Université de Paris, Paris, France
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Klinički Centar Niš, Klinika za dečije interne bolesti – Odeljenje za nefrologiju, Niš, Serbia
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