Hydrochlorothiazide for Polycystic Kidney Disease

(HYDRO-PROTECT Trial)

Not yet recruiting at 16 trial locations

Overseen By T. Bais, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University Medical Center Groningen

Must be taking: V2RA

Must not be taking: Diuretics

Disqualifiers: Gout, Skin cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 156 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for autosomal dominant polycystic kidney disease (ADPKD), a condition where cysts form in the kidneys and can lead to kidney failure. Researchers aim to determine if adding hydrochlorothiazide, a common blood pressure medication, to the current treatment (Tolvaptan) can slow kidney damage and improve patients' quality of life. Participants will take hydrochlorothiazide or a placebo daily for about three years. This trial may suit individuals diagnosed with ADPKD who have been on stable V2RA treatment for at least three months and have not experienced issues with hydrochlorothiazide. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you are already on a stable treatment with the highest tolerated dose of Tolvaptan for at least 3 months. You cannot participate if you are using any diuretics or have certain conditions like uncontrolled hypertension or active gout on preventive treatment.

Is there any evidence suggesting that hydrochlorothiazide is likely to be safe for humans?

Research has shown that hydrochlorothiazide is generally well-tolerated. A study on thiazide diuretics, such as hydrochlorothiazide, found that they do not worsen polycystic kidney disease, suggesting safety for this condition. Additionally, compared to a similar drug, chlorthalidone, hydrochlorothiazide is associated with a lower risk of kidney problems, indicating it might be the safer choice. Overall, evidence suggests that hydrochlorothiazide is a well-tolerated option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney disease?

Unlike the standard treatments for polycystic kidney disease, which often focus on managing blood pressure and addressing symptoms, hydrochlorothiazide offers a different approach. This medication works as a diuretic, helping the kidneys eliminate excess fluid and salt from the body, which can potentially alleviate the burden on the kidneys and slow disease progression. Researchers are particularly excited about hydrochlorothiazide because it offers a well-tolerated option that could complement existing therapies, providing a fresh way to manage this challenging condition.

What evidence suggests that hydrochlorothiazide might be an effective treatment for ADPKD?

This trial will evaluate the effectiveness of hydrochlorothiazide for polycystic kidney disease. Research has shown that hydrochlorothiazide, a medication that helps the body remove extra salt and water, might enhance the effectiveness of tolvaptan in treating autosomal dominant polycystic kidney disease (ADPKD). Studies indicate that hydrochlorothiazide does not worsen ADPKD, suggesting it could be a safe addition to tolvaptan treatment. The goal is to slow kidney damage and improve patients' quality of life by reducing side effects like excessive urination. While more research is needed, these early findings are promising for better managing ADPKD. ^{1 2 5 6 7}

Who Is on the Research Team?

Prof. dr. R.T. Gansevoort

Principal Investigator

University Medical Center Groningen

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Polycystic Kidney Disease (ADPKD) who have a certain level of kidney function and have been on Tolvaptan treatment. It's not for those allergic to Hydrochlorothiazide, using other diuretics, with very low or high blood pressure, low potassium levels, frequent gout attacks, or a history of skin cancer.

Inclusion Criteria

I have been on a stable dose of my heart medication for at least 3 months.

I have been diagnosed with ADPKD.

Your kidney function is better than a certain level.

Exclusion Criteria

I have low blood pressure or feel dizzy when standing up.

I have had gout attacks more than twice last year and am on preventive medication.

My blood pressure is not higher than 160/100 mmHg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral hydrochlorothiazide 25 mg or matching placebo once daily

156 weeks

12-weekly visits, plus one additional visit or call 2 weeks after treatment start

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hydrochlorothiazide

Trial Overview The study tests if adding Hydrochlorothiazide to the current ADPKD treatment with Tolvaptan can better slow down kidney decline and improve life quality. About 300 patients will either receive the drug or a placebo in addition to their standard care.

How Is the Trial Designed?

Group I: Hydrochlorothiazide Active Control 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Hydrochlorothiazide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Hydrochlorothiazide for:

• Edema
• Hypertension
• Nephrotic syndrome
• Nephritic syndrome
• Gouty arthritis
• Calcium nephrolithiasis

Approved in European Union as Hydrochlorothiazide for:

• Essential hypertension
• Oedema

Approved in Canada as Hydrochlorothiazide for:

• Mild to moderate hypertension
• Edema

Approved in Japan as Hydrochlorothiazide for:

• Hypertension
• Edema

Who Is Running the Clinical Trial?

University Medical Center Groningen

Lead Sponsor

Trials

770

Recruited

1,101,000+

Published Research Related to This Trial

Thiazide diuretics are established as first-line treatments for hypertension and can be used alone or in combination with other medications, but their use in patients with advanced chronic kidney disease (CKD) is often avoided due to safety and efficacy concerns.

An updated review by Minutolo et al. examines the pharmacological properties and clinical trial data of thiazide diuretics in CKD patients, suggesting that these medications may still be effective and safe despite the reluctance to prescribe them in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiazides in chronic kidney disease: "back to the future". de la Espriella, R., Cobo, M., Núñez, J.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10865620/

HYDROchlorothiazide versus placebo to PROTECT ... The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05373264

HYDROchlorothiazide to PROTECT Polycystic Kidney ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8476080/

Thiazide diuretics and the rate of disease progression in ... These data do not show that thiazide diuretics have a detrimental effect on the rate of disease progression in ADPKD and suggest that these drugs can be ...

4. pure.eur.nl pure.eur.nl/files/137029515/HYDROchlorothiazide_versus_placebo_to_PROTECT_polycystic_kidney_disease_patients_and_improve_their_quality_of_life.pdf

HYDROchlorothiazide versus placebo to PROTECT ... We have designed the HYDRO-PROTECT study. (HYDROchlorothiazide to PROTECT polycystic kidney disease patients and improve their quality of life) ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2827625

Chlorthalidone vs Hydrochlorothiazide and Kidney ... Several observational studies comparing chlorthalidone with hydrochlorothiazide have suggested an increased risk of acute kidney injury and ...

6. academic.oup.com academic.oup.com/ndt/article/36/10/1828/5956378

Thiazide diuretics and the rate of disease progression in ... These data do not show that thiazide diuretics have a detrimental effect on the rate of disease progression in ADPKD and suggest that these drugs can be ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34524440/

Comparison of Clinical Outcomes and Safety Associated ... This cohort study found that among older adults, chlorthalidone use was associated with a higher risk of eGFR decline, cardiovascular events ...