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.
ADPKD diagnosis (modified Ravine criteria)
≥18 years old
eGFR > 25 mL/min/1.73m2
On stable treatment with the highest tolerated dose of V2RA for a minimum of 3 months
Known intolerance to hydrochlorothiazide
Use of any diuretic
Orthostatic hypotension complaints or blood pressure <105/65mmHg during screening visit
Uncontrolled hypertension (blood pressure >160/100mmHg)
Parallel
Hydrochlorothiazide 25 mg
DrugAn oral capsule containing 25mg of hydrochlorothiazide
Placebo
DrugA 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.
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)
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)
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)
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)
Click on the lead sponsor to view all of their trials.