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NCT Number: NCT05373264

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

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.

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Key information

Conditions

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

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Cliniques Universitaires Saint-Luc, Brussels, Belgium

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About this study

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)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Hydrochlorothiazide 25 mg

Drug

An oral capsule containing 25mg of hydrochlorothiazide

Placebo

Drug

A matching oral capsule containing placebo

Primary outcomes

  1. Changes in kidney function decline

    Time frame: 156 weeks

    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.

Secondary outcomes

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

    Time frame: 168 weeks

    A secondary outcome is the change in eGFR from baseline compared to end of study (12 weeks after end of treatment)

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

    Time frame: 168 weeks

    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)

  3. Changes in 24-hour urine volume

    Time frame: 156 weeks

    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)

  4. Quality of life, assessed by the TIPS questionnaire

    Time frame: 156 weeks

    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)

  5. Quality of life, assessed by the ADPKD-UIS questionnaire

    Time frame: 156 weeks

    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)

  6. Quality of life, assessed by the SF-12 questionnaire

    Time frame: 156 weeks

    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)

  7. Quality of life, assessed by the EQ-5D questionnaire

    Time frame: 156 weeks

    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)

  8. Change in V2RA dose

    Time frame: 168 weeks

    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

  9. Change in V2RA discontinuation rate

    Time frame: 168 weeks

    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

  10. Changes in serum sodium concentration

    Time frame: 168 weeks

    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)

  11. Changes in serum potassium concentration

    Time frame: 168 weeks

    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)

  12. Changes in plasma serum calcium concentration

    Time frame: 168 weeks

    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)

  13. Changes in serum phosphate concentration

    Time frame: 168 weeks

    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)

  14. Incidence of (serious) adverse events

    Time frame: 168 weeks

    Incidence of (serious) adverse events from baseline until the end of study (12 weeks after end of treatment)

Study contacts

Contact information is provided by the study sponsor or research team.

Dr. E Meijer

CONTACT

[email protected]

+31 50 3616161

T. Bais, MD

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

University Medical Center Groningen

Other

Registry information

Acronym: HYDRO-PROTECT

Important dates

Study start
2024
Primary completion
2030
Study completion
2031
First posted
May 13, 2022
Registry last updated
Feb 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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