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

Autor: Aurélia Bertholet-Thomas, Catherine Guittet, Maria A. Manso-Silván, Arnaud Castang, Véronique Baudouin, Mathilde Cailliez, Massimo Di Maio, Olivia Gillion-Boyer, Emilija Golubovic, Jérôme Harambat, Alexandre Klein, Bertrand Knebelmann, François Nobili, Robert Novo, Ludmila Podracka, Gwenaëlle Roussey-Kesler, Christos Stylianou, Luc-André Granier
Přispěvatelé: Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Hôpital Robert Debré, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpitaux Civils de Colmar, Hôpital Necker, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Pediatric Nephrology
Pediatric Nephrology, Springer Verlag, 2021, 36 (1), pp.83-91. ⟨10.1007/s00467-020-04693-2⟩
Pediatr Nephrol
Pediatric Nephrology (Berlin, Germany)
ISSN: 0931-041X
1432-198X
DOI: 10.1007/s00467-020-04693-2⟩
Popis: 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 p = 0.0008, intention to treat [ITT]), and the response rate increased from 43 to 90% with ADV7103 (p p = 0.021, ITT). Palatability was improved (difference [95% CI] of 25 [10.7, 39.2] mm) and gastrointestinal discomfort was reduced (difference [95% CI] of − 14.2 [− 25.9, − 2.6] mm) with ADV7103. Conclusions Plasma bicarbonate levels and response rate were significantly higher with ADV7103 than with SoC. Urine calcium/citrate ratio, palatability, and gastrointestinal safety were significantly improved, supporting the use of ADV7103 as first-line treatment for dRTA. Trial registration Registered as EudraCT 2013-002988-25 on the 1st July 2013
Databáze: OpenAIRE
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