ADPKDPhase 3HYDRO-PROTECTNCT05373264
HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
A Phase 3 study testing Hydrochlorothiazide 25 mg in people with ADPKD, run by University Medical Center Groningen at 25 sites in 7 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- ADPKD
- What is being tested?
- Hydrochlorothiazide 25 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 25 sitesin 7 countries
- Study dates
- 31 Jul 2024to Jul 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
- Hypokalemia (<3.5 mmol/L)
- History of active gout on maintenance preventive treatment for gout (allopurinol, desuric and/or colchicine), defined as ≥2 episodes during the last year
- History of skin cancer (basal cell, squamous cell and melanoma)
Trial locations and contacts
25 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
T. Bais, MD contact
25 sites in 7 countries
France5 sites, 5 recruiting
- Recruiting
Hôpital Pellegrin (CHU Bordeaux)
Bordeaux
Claire Rigothier
- Recruiting
Hospital La Cavale Blanche
Brest
Prof. dr. E. Cornec-Le Gall
- Recruiting
Centre Hôpital Universitaire de Lyon
Lyon
Sandrine Lemoine
- Recruiting
Hôpitaux de Brabois (CHRU)
Nancy
Adrien Flahault
- Recruiting
Necker-Enfants Malades Hospital
Paris
Prof dr. B. Knebelmann
Germany4 sites, 4 recruiting
- Recruiting
Charité University Hospital
Berlin
Prof J. Halbritter
- Recruiting
University Hospital Cologne
Cologne
Prof. dr. R.U. Müller
- Recruiting
Med. Klinik und Poliklinik III, Universitätsklinikum Dresden.
Dresden
Alexander Paliege
- Recruiting
Universitätsklinikum Leipzig
Leipzig
Friederike Petzold, dr.
Spain4 sites, 4 recruiting
- Recruiting
Hospital Universitario Mancha Centro
Alcázar de San Juan
Rebeca Garcia
- Recruiting
Fundación Puigvert
Barcelona
Prof. dr. R. Torra
- Recruiting
Hospital Universitario Vall D'Hebron
Barcelona
Laia Sans
- Recruiting
La Fundación Jiménez Díaz
Madrid
María Vanessa Pérez Gómez
Switzerland4 sites, 4 recruiting
- Recruiting
Universitätsspital Bern (Inselsspital)
Bern
Daniel Fuster
- Recruiting
Hôpital Fribourgeois (HFR)
Fribourg
Olivier Bonny
- Recruiting
Hôpitaux Universitaires de Genève (HUG)
Geneva
Fadi Haidar
- Recruiting
Universitätsspital Zürich (USZ)
Zurich
Andrea Viecelli
Belgium3 sites, 3 recruiting
- Recruiting
Universitair Ziekenhuis Antwerpen (UZA)
Antwerp
Paulien Lievens
Rowena Vleut
- Recruiting
Cliniques Universitaires Saint-Luc
Brussels
Prof. Nathalie Demoulin
- Recruiting
University Hospital Leuven
Leuven
Prof dr. B. Bammens
Netherlands3 sites, 3 recruiting
- Recruiting
Amsterdam University Medical Center
Amsterdam
Prof dr. M. van Ittersum
- Recruiting
University Medical Center Groningen
Groningen
dr. T Bais, t.bais@umcg.nl
- Recruiting
Erasmus University Medical Center
Rotterdam
dr. M. Salih
Austria2 sites, 2 recruiting
- Recruiting
Uniklinikum Graz
Graz
Werner Ribitsch, dr.
- Recruiting
Medizinische Universität Innsbruck
Innsbruck
Michael Rudnicki, prof.
About this study
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.
Read the detailed description
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)
- Conditions
- ADPKD
- Being tested
- Hydrochlorothiazide 25 mg, Placebo
- Keywords
- ADPKD, Tolvaptan, Hydrochlorothiazide, Quality of Life, Side effects, Polyuria
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant, Polyuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydrochlorothiazide 25 mgDrug
An oral capsule containing 25mg of hydrochlorothiazide
PlaceboDrug
A matching oral capsule containing placebo
| Study group | Role | What they receive |
|---|---|---|
| Hydrochlorothiazide | Active comparator | Oral hydrochlorothiazide 25mg, once daily, for a total of 156 weeks Receives: Drug: Hydrochlorothiazide 25 mg |
| Placebo | Placebo comparator | Matching oral placebo, once daily, for a total of 156 weeks. The placebo is inert. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 156 weeks
Secondary outcomes (14)
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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 168 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2022
- Study start31 Jul 2024
- Primary completionJul 2030 (estimated)
- Study completionJul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ADPKDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- An investigator driven, multicenter, placebo-controlled, randomized clinical trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Prof. dr. R.T. Gansevoort, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05373264
- Sponsor's protocol ID
- 202100714
- Other IDs
- 2021-005612-61
- Acronym
- HYDRO-PROTECT
- Status last verified
- Feb 2026
- First submitted
- 28 Apr 2022
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No