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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

Authors
  • Bertholet-Thomas, Aurélia1
  • Guittet, Catherine2
  • Manso-Silván, Maria A.2
  • Castang, Arnaud2
  • Baudouin, Véronique3
  • Cailliez, Mathilde4
  • Di Maio, Massimo5
  • Gillion-Boyer, Olivia6
  • Golubovic, Emilija7
  • Harambat, Jérôme8
  • Klein, Alexandre9
  • Knebelmann, Bertrand10
  • Nobili, François11
  • Novo, Robert12
  • Podracka, Ludmila13
  • Roussey-Kesler, Gwenaëlle14
  • Stylianou, Christos15
  • Granier, Luc-André2
  • 1 Hospices Civils de Lyon, Bron, France , Bron (France)
  • 2 Advicenne, Nîmes, France , Nîmes (France)
  • 3 Hôpital Robert Debré, Paris, France , Paris (France)
  • 4 Hôpital de la Timone, AP-HM, Marseille, France , Marseille (France)
  • 5 CHU de Nîmes, Nîmes, France , Nîmes (France)
  • 6 Université de Paris, Paris, France , Paris (France)
  • 7 Klinički Centar Niš, Klinika za dečije interne bolesti – Odeljenje za nefrologiju, Niš, Serbia , Niš (Serbia)
  • 8 Service de Pédiatrie, CHU de Bordeaux, Hôpital Pellegrin-Enfants, Bordeaux, France , Bordeaux (France)
  • 9 Service de Néphrologie, Pôle DIACOR, Hôpitaux Civils de Colmar, Colmar, France , Colmar (France)
  • 10 Service de Néphrologie adultes Hôpital Necker, Paris, France , Paris (France)
  • 11 Service de Pédiatrie 2, Hôpital Jean Minjoz, CHU de Besançon, Besançon, France , Besançon (France)
  • 12 Service de Néphrologie Pédiatrique, Hôpital Jeanne de Flandre, CHRU de Lille, Lille, France , Lille (France)
  • 13 National Institute of Children’s Health, Bratislava, Slovakia , Bratislava (Slovakia)
  • 14 CHU de Nantes, Nantes, France , Nantes (France)
  • 15 ClinBay Ltd., Limassol, Cyprus , Limassol (Cyprus)
Type
Published Article
Journal
Pediatric Nephrology
Publisher
Springer-Verlag
Publication Date
Jul 26, 2020
Volume
36
Issue
1
Pages
83–91
Identifiers
DOI: 10.1007/s00467-020-04693-2
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundDistal 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.MethodsIn 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.ResultsWhen 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) and gastrointestinal discomfort was reduced (difference [95% CI] of − 14.2 [− 25.9, − 2.6] mm) with ADV7103.ConclusionsPlasma 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 registrationRegistered as EudraCT 2013-002988-25 on the 1st July 2013Graphical abstract

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