HYDROchlorothiazide versus placebo to PROTECT polycystic kidney disease patients and improve their quality of life: study protocol and rationale for the HYDRO-PROTECT randomized controlled trial

Abstract

Background

Autosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a preliminary clinical study, the addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-h urinary volume and appeared to increase renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in patients with ADPKD.

Methods

The HYDRO-PROTECT study is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. The study is powered to enroll 300 rapidly progressive patients with ADPKD aged ≥ 18 years, with an eGFR of > 25 mL/min/1.73 m2, and on stable treatment with the highest tolerated dose of tolvaptan in routine clinical care. Patients will be randomly assigned (1:1) to daily oral HCT 25 mg or matching placebo treatment for 156 weeks, in addition to standard care.

Outcomes

The primary study outcome is the rate of kidney function decline (expressed as eGFR slope, in mL/min/1.73 m2 per year) in HCT versus placebo-treated patients, calculated by linear mixed model analysis using all available creatinine values from week 12 until the end of treatment. Secondary outcomes include changes in quality-of-life questionnaire scores (TIPS, ADPKD-UIS, EQ-5D-5L, SF-12) and changes in 24-h urine volume.

Conclusion

The HYDRO-PROTECT study will demonstrate whether co-treatment with HCT can improve the renoprotective efficacy and tolerability of tolvaptan in patients with ADPKD.

Metadata

Item Type:	Article
Authors/Creators:	Bais, T. Meijer, E. https://orcid.org/0000-0001-7875-1793 Kramers, B.J. Vart, P. Vervloet, M. Salih, M. Bammens, B. Demoulin, N. Todorova, P. Müller, R.-U. Halbritter, J. Paliege, A. Gall, E.C.-L. Knebelmann, B. Torra, R. Ong, A.C.M. https://orcid.org/0000-0002-7211-5400 Karet Frankl, F.E. Gansevoort, R.T.
Copyright, Publisher and Additional Information:	© 2024 The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecom‑ mons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Dates:	Published: December 2024 Published (online): 14 February 2024 Accepted: 24 January 2024 Submitted: 18 July 2023
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health
Depositing User:	Symplectic Sheffield
Date Deposited:	21 Feb 2024 12:46
Last Modified:	21 Feb 2024 12:46
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1186/s13063-024-07952-x
Related URLs:	Dataset
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:209384