HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life

NCT05373264 | Recruiting Phase 3 DMC

• 2 other identifiers: 2021007142021-005612-61
• Study Type: interventional
• Target: 300
• Locations: 5 countries
• Sites: 12

Brief 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. 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.

Conditions

ADPKD

Keywords

ADPKD; Tolvaptan; Hydrochlorothiazide; Quality of Life; Side effects; Polyuria

Outcome Measures

Primary Outcomes (1)

• 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.

  156 weeks

Secondary Outcomes (14)

• Changes in eGFR from baseline compared to end of study (12 weeks after End of Treatment)

  168 weeks

• Incidence of 30% decrease in eGFR, end stage kidney disease (EKSD) or renal death

  168 weeks

• Changes in 24-hour urine volume

  156 weeks

• Quality of life, assessed by the TIPS questionnaire

  156 weeks

• Quality of life, assessed by the ADPKD-UIS questionnaire

  156 weeks

Study Arms (2)

Hydrochlorothiazide

ACTIVE COMPARATOR

Oral hydrochlorothiazide 25mg, once daily, for a total of 156 weeks

Drug: Hydrochlorothiazide 25 mg

Placebo

PLACEBO COMPARATOR

Matching oral placebo, once daily, for a total of 156 weeks. The placebo is inert.

Drug: Placebo

Interventions

Hydrochlorothiazide 25 mg DRUG

An oral capsule containing 25mg of hydrochlorothiazide

Hydrochlorothiazide

Placebo DRUG

A matching oral capsule containing placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (12)

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

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Polyuria

Interventions

Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Prof. dr. R.T. Gansevoort

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr. E Meijer

CONTACT

+31 50 3616161; esther.meijer@umcg.nl

T. Bais, MD

CONTACT

t.bais@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: An investigator driven, multicenter, placebo-controlled, randomized clinical trial.

Study Record Dates

• First Submitted: April 28, 2022
• First Posted: May 13, 2022
• Study Start: July 31, 2024
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2031
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); FR (2); NL (3); ES (2); DE (3)