Hydrochlorothiazide for Polycystic Kidney Disease

(HYDRO-PROTECT Trial)

Recruiting at 14 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

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if adding hydrochlorothiazide, a common blood pressure medication, to the existing kidney disease treatment Tolvaptan can improve its effectiveness and reduce side effects. The study targets adults with a specific type of kidney disease who are already on Tolvaptan. Tolvaptan helps slow kidney damage but can cause excessive urination, and hydrochlorothiazide might help manage this issue. Tolvaptan is the only approved drug for this type of kidney disease and has been shown to slow its progression.

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 hydrochlorothiazide safe for humans?

Hydrochlorothiazide has been used for over 60 years to manage high blood pressure and is generally considered safe, but it may increase the risk of skin cancer and cause adverse effects on the kidneys, especially at high doses or in people with existing kidney issues. ^{1 2 3 4 5}

How is the drug Hydrochlorothiazide unique for treating polycystic kidney disease?

Hydrochlorothiazide is unique for treating polycystic kidney disease because it can reduce the excessive urination caused by another treatment, tolvaptan, which is commonly used for this condition. This makes it a potentially valuable addition to manage side effects in patients undergoing tolvaptan therapy. ^{3 5 6 7 8}

Research Team

Prof. dr. R.T. Gansevoort

Principal Investigator

University Medical Center Groningen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Toxicology and carcinogenicity studies of diuretics in F344 rats and B6C3F1 mice. 1. Hydrochlorothiazide. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Thiazide diuretics and the rate of disease progression in autosomal dominant polycystic kidney disease: an observational study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Thiazides in chronic kidney disease: "back to the future". [2023]

4. England pubmed.ncbi.nlm.nih.gov

Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of hydrochlorothiazide on urinary calcium excretion in dent disease: an uncontrolled trial. [2013]

6. Australia pubmed.ncbi.nlm.nih.gov

Severe hyperkalaemia with Moduretic. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Hydrochlorothiazide is not the most useful nor versatile thiazide diuretic. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

Hydrochlorothiazide ameliorates polyuria caused by tolvaptan treatment of polycystic kidney disease in PCK rats. [2021]