A Phase 3 interventional study of Hydrochlorothiazide 25 mg and Placebo in ADPKD, sponsored by University Medical Center Groningen. Recruiting at 25 sites in 7 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by University Medical Center Groningen · Phase 3, Interventional, and Treatment
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive formation of renal cysts which ultimately lead to a loss of renal function.
Tolvaptan (a V2R antagonist) is currently the only effective treatment for preserving renal function in ADPKD. However, side-effects such as polyuria limit its tolerability and thereby the therapeutic potential. This study will test whether co-administration with hydochlorothiazide can improve V2RA efficacy (slowing kidney function decline) and tolerability (quality of life) in ADPKD. Approximately 300 patients will be enrolled.
Aims: The main objectives of the current study are to prospectively test whether HCT co-treatment can improve V2RA efficacy (slowing kidney function decline) and tolerability (quality of life) in PKD.
Study design: Investigator driven randomized placebo-controlled multicenter trial
Study population: 300 ADPKD patients of ≥18 years, with an eGFR of > 25 mL/min/1.73m2, on stable treatment with the highest tolerated dose of V2RA
Intervention: Oral HCT 25 mg once daily or matching placebo for a total of 156 weeks. The randomization ratio will be 1:1.
Study visit schedule: study measurements will be performed during 12-weekly visits (which is routine care for V2RA treated patients), except for one additional study visit (or telephone call) 2 weeks after the start of treatment
Primary study outcome: Slope of kidney function decline (measured by eGFR)
185 studies on the registry are indexed under Polycystic Kidney, Autosomal Dominant; 42 are open to participants now.
This study's planned enrollment of 300 is above the median of 51 across 138 interventional studies indexed under Polycystic Kidney, Autosomal Dominant.
Browse Polycystic Kidney, Autosomal Dominant studies →University Medical Center Groningen is the lead sponsor of 627 studies on the registry; 176 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Oral hydrochlorothiazide 25mg, once daily, for a total of 156 weeks
Drug: Hydrochlorothiazide 25 mg
Matching oral placebo, once daily, for a total of 156 weeks. The placebo is inert.
Drug: Placebo
An oral capsule containing 25mg of hydrochlorothiazide
A matching oral capsule containing placebo
Changes in kidney function decline
The primary outcome is the change in kidney function decline (assessed as eGFR slope, in ml/min/1.73 m2 per year), calculated with linear mixed models, using all available creatinine values from week 12 until end of treatment between the tolvaptan/placebo and tolvaptan/HCT group.
Time frame: 156 weeks
Changes in eGFR from baseline compared to end of study (12 weeks after End of Treatment)
A secondary outcome is the change in eGFR from baseline compared to end of study (12 weeks after end of treatment)
Time frame: 168 weeks
Incidence of 30% decrease in eGFR, end stage kidney disease (EKSD) or renal death
A secondary outcome is the incidence of a 30% decrease in eGFR, occurrence of end stage kidney disease (EKSD) or renal death during the entire study period (until the end of study (12 weeks after end of treatment)
Time frame: 168 weeks
Changes in 24-hour urine volume
A secondary outcome is the change in 24-hour urine volume, measured at baseline, week 12, week 48, week 96 and week 156 (end of treatment)
Time frame: 156 weeks
Quality of life, assessed by the TIPS questionnaire
Changes in Quality of Life measured by the Tolvaptan Impact of Polyuria Scale questionnaire (TIPS) at baseline, week 12, week 48, week 96 and week 156 (end of treatment)
Time frame: 156 weeks
Quality of life, assessed by the ADPKD-UIS questionnaire
Changes in Quality of Life measured by the ADPKD-Urinary Impact Scale questionnaire (ADPKD-UIS) at baseline, week 12, week 48, week 96 and week 156 (end of treatment)
Time frame: 156 weeks
Quality of life, assessed by the SF-12 questionnaire
Changes in Quality of Life measured by the Short Form 12 questionnaire (SF-12) at baseline, week 12, week 48, week 96 and week 156 (end of treatment)
Time frame: 156 weeks
Quality of life, assessed by the EQ-5D questionnaire
Changes in Quality of Life measured by the EuroQol-5 Dimension questionnaire (EQ-5D) at baseline, week 12, week 48, week 96 and week 156 (end of treatment)
Time frame: 156 weeks
Change in V2RA dose
V2RA dose during each study visit and compared at the end of study visit (12 weeks after end of treatment) between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group
Time frame: 168 weeks
Change in V2RA discontinuation rate
The V2RA discontinuation rate will be compared at the end of study visit (12 weeks after end of treatment) between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group
Time frame: 168 weeks
Changes in serum sodium concentration
Changes in serum sodium concentration between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group, measured from baseline until the end of study (12 weeks after end of treatment)
Time frame: 168 weeks
Changes in serum potassium concentration
Changes in serum potassium concentration between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group, measured from baseline until the end of study (12 weeks after end of treatment)
Time frame: 168 weeks
Changes in plasma serum calcium concentration
Changes in plasma serum calcium concentration between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group, measured from baseline until the end of study (12 weeks after end of treatment)
Time frame: 168 weeks
Changes in serum phosphate concentration
Changes in serum phosphate concentration between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group, measured from baseline until the end of study (12 weeks after end of treatment)
Time frame: 168 weeks
Incidence of (serious) adverse events
Incidence of (serious) adverse events from baseline until the end of study (12 weeks after end of treatment)
Time frame: 168 weeks
Plan to share: No
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Started Jul 2024 (actual). Primary completion is estimated for Jul 2030, 72 months after the start.
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Studies of the drug tested here: Hydrochlorothiazide
Polycystic Kidney, Autosomal Dominant →
University Medical Center Groningen →