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) 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 Graphical abstract.

中文翻译：

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创新型缓释组合药物对远端肾小管酸中毒患者的疗效和安全性：一项与标准护理治疗的开放标签比较试验。


背景技术 由于尿液中酸分泌受损，远端肾小管酸中毒（dRTA）可导致严重的长期后果。标准护理 (SoC) 口服碱化剂需要每天摄入几次，目前用于恢复正常的血浆碳酸氢盐水平。一种新的缓释制剂 ADV7103 已被开发出来，通过改进的剂量方案实现持续的效果。方法 在一项多中心、开放标签、非劣效性试验 (n = 37) 中，接受 dRTA 的患者从 SoC 转为 ADV7103。比较了两种治疗方法稳态治疗期间的平均血浆碳酸氢盐值和反应者比例，以及其他血液和尿液参数，以及可接受性、耐受性和安全性。结果 当从 SoC 切换到 ADV7103 时，每日摄入次数从平均每天 3 次减少到每天两次。平均血浆碳酸氢盐增加，并且证明了 ADV7103 的非劣效性（p < 0.0001，每个方案），以及统计优越性（p = 0.0008，意向治疗 [ITT]），并且响应率从 43% 增加到 90% ADV7103（p < 0.001，ITT）。使用 ADV7103，56% 先前使用 SoC 无反应的患者中，尿钙/柠檬酸盐比率降低至成石风险阈值以下（p = 0.021，ITT）。 ADV7103 的适口性得到改善（差异 [95% CI] 为 25 [10.7, 39.2] mm），胃肠不适减少（差异 [95% CI] 为 - 14.2 [- 25.9, - 2.6] mm）。结论 ADV7103 的血浆碳酸氢盐水平和反应率显着高于 SoC。尿钙/柠檬酸盐比、适口性和胃肠道安全性显着改善，支持使用 ADV7103 作为 dRTA 的一线治疗。 试用注册 于 2013 年 7 月 1 日注册为 EudraCT 2013-002988-25 图解摘要。