TY - JOUR
T1 - HYDROchlorothiazide versus placebo to PROTECT polycystic kidney disease patients and improve their quality of life :
T2 - study protocol and rationale for the HYDRO-PROTECT randomized controlled trial
AU - Bais, T.
AU - Meijer, E.
AU - Kramers, B.J.
AU - Vart, P.
AU - Vervloet, M.
AU - Salih, M.
AU - Bammens, B.
AU - Demoulin, N.
AU - Todorova, P.
AU - Müller, R.U.
AU - Halbritter, J.
AU - Paliege, A.
AU - Gall, E.C.L.
AU - Knebelmann, B.
AU - Torra, Roser
AU - Ong, A.C.M.
AU - Karet Frankl, F.E.
AU - Gansevoort, R.T.
PY - 2024/2/14
Y1 - 2024/2/14
N2 - 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 m
2, 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 m
2 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.
AB - 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 m
2, 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 m
2 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.
KW - Antidiuretic Hormone Receptor Antagonists
KW - Glomerular Filtration Rate
KW - Humans
KW - Hydrochlorothiazide
KW - Kidney
KW - Multicenter Studies as Topic
KW - Polycystic Kidney, Autosomal Dominant
KW - Quality of Life
KW - Randomized Controlled Trials as Topic
KW - Tolvaptan
UR - http://www.scopus.com/inward/record.url?scp=85185268100&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/cee9fcff-2af6-3a5b-94c9-1b7ac69f52fe/
U2 - 10.1186/s13063-024-07952-x
DO - 10.1186/s13063-024-07952-x
M3 - Article
C2 - 38355627
SN - 1745-6215
VL - 25
JO - Trials
JF - Trials
IS - 1
M1 - 120
ER -