Hydrochlorothiazide added to tolvaptan to protect kidneys and improve quality of life in ADPKD
HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
This trial tests whether adding low-dose hydrochlorothiazide to adults with ADPKD who are already taking tolaptan slows kidney decline and reduces side effects like excessive urination.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 300 (estimated) |
| Ages | 18 Years to 80 Years |
| Sex | All |
| Sponsor | University Medical Center Groningen Academic / other |
| Locations | 12 sites (Brussels and 11 other locations) |
| Trial ID | NCT05373264 on ClinicalTrials.gov |
What this trial studies
This is an investigator-driven, randomized, placebo-controlled multicenter Phase 3 trial enrolling about 300 adults with ADPKD who are on a stable, highest tolerated dose of a V2 receptor antagonist (tolvaptan). Participants are randomized 1:1 to receive oral hydrochlorothiazide 25 mg once daily or matching placebo for 156 weeks. The primary outcome is the slope of kidney function decline measured by eGFR, with routine study visits every 12 weeks and one additional visit or phone call two weeks after starting treatment. The design aims to measure both efficacy on kidney function and effects on tolerability and quality of life compared with placebo.
Who should consider this trial
Good fit: Adults (≥18 years) with a diagnosis of ADPKD, eGFR >25 mL/min/1.73m2, who have been on a stable, highest tolerated dose of a V2 receptor antagonist (tolvaptan) for at least three months are eligible.
Not a fit: Patients with known hydrochlorothiazide intolerance, current diuretic use, low blood pressure, significant electrolyte abnormalities, recent active gout, a history of skin cancer, or eGFR ≤25 mL/min/1.73m2 are unlikely to be eligible or benefit from this intervention.
Why it matters
Potential benefit: If successful, adding hydrochlorothiazide could slow kidney function loss and improve tolerability of tolvaptan by reducing bothersome polyuria, which may improve patients' quality of life.
How similar studies have performed: Physiologic and small observational reports suggest thiazides can reduce polyuria and may improve tolaptan tolerability, but large randomized trials in ADPKD are currently lacking.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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)
Where this trial is running
Brussels and 11 other locations
- Cliniques Universitaires Saint-Luc — Brussels, Belgium (Recruiting)
- University Hospital Leuven — Leuven, Belgium (Recruiting)
- Hospital La Cavale Blanche — Brest, France (Recruiting)
- Necker-Enfants Malades Hospital — Paris, France (Recruiting)
- Charité University Hospital — Berlin, Germany (Recruiting)
- University Hospital Cologne — Cologne, Germany (Recruiting)
- Med. Klinik und Poliklinik III, Universitätsklinikum Dresden. — Dresden, Germany (Recruiting)
- Amsterdam University Medical Center — Amsterdam, Netherlands (Recruiting)
- University Medical Center Groningen — Groningen, Netherlands (Recruiting)
- Erasmus University Medical Center — Rotterdam, Netherlands (Recruiting)
- Fundación Puigvert — Barcelona, Spain (Recruiting)
- La Fundación Jiménez Díaz — Madrid, Spain (Recruiting)
Study contacts
- Principal investigator: Prof. dr. R.T. Gansevoort — University Medical Center Groningen
- Study coordinator: Dr. E Meijer
- Email: esther.meijer@umcg.nl
- Phone: +31 50 3616161
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.