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
Thomas Bais,
Esther Meijer,
Bart J. Kramers,
Priya Vart,
Marc Vervloet,
Mahdi Salih,
Bert Bammens,
Nathalie Demoulin,
Polina Todorova,
Roman-Ulrich Müller,
Jan Halbritter,
Alexander Paliege,
Emilie Cornec-Le Gall,
Bertrand Knebelmann,
Roser Torra,
Albert C. M. Ong,
Fiona E. Karet Frankl,
Ron T. Gansevoort
Affiliations
Thomas Bais
Department of Nephrology, University Medical Center Groningen
Esther Meijer
Department of Nephrology, University Medical Center Groningen
Bart J. Kramers
Department of Nephrology, University Medical Center Groningen
Priya Vart
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen
Marc Vervloet
Department of Nephrology, Amsterdam University Medical Centers, Location Vrije Universiteit Amsterdam
Mahdi Salih
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus University Medical Center
Bert Bammens
Department of Nephrology, Dialysis and Renal Transplantation, University Hospitals Leuven
Nathalie Demoulin
Division of Nephrology, Cliniques Universitaires Saint-Luc
Polina Todorova
University of Cologne, Faculty of Medicine and University Hospital Cologne, Department 2 for Internal Medicine
Roman-Ulrich Müller
University of Cologne, Faculty of Medicine and University Hospital Cologne, Department 2 for Internal Medicine
Jan Halbritter
Department of Nephrology, Charité Universitätsmedizin Berlin
Alexander Paliege
Department of Nephrology, Universitätsklinikum Carl Gustav Carus Dresden
Emilie Cornec-Le Gall
University Brest, Inserm, UMR 1078, GGB
Bertrand Knebelmann
Department of Nephrology, Necker–Enfants Malades Hospital AP-HP
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.
