What side effects are associated with this type of intervention?

Tolvaptan, a V2R antagonist used in the treatment of Polycystic Kidney Disease (PKD), is associated with side effects such as increased liver enzymes, chest pain, headache, hyperuricemia, gout, and significant polyuria, which can limit its tolerability. Hydrochlorothiazide, a thiazide diuretic, commonly causes side effects like electrolyte imbalances (e.g., decreased potassium), increased uric acid levels, and potential metabolic changes. Both medications require careful monitoring to manage these adverse effects effectively.

What prior FDA approvals exist?

Tolvaptan, a vasopressin V2 receptor antagonist, is currently the only FDA-approved treatment specifically for Autosomal Dominant Polycystic Kidney Disease (ADPKD). It is used to slow the decline of kidney function in affected patients. Hydrochlorothiazide, a thiazide diuretic, is being studied in combination with Tolvaptan to improve its efficacy and tolerability, although it is not yet FDA-approved for this specific use in ADPKD. These treatments aim to manage symptoms and slow disease progression by addressing fluid balance and kidney function.

What other types of research exist?

Promising novel alternatives for Polycystic Kidney Disease patients include angiotensin II receptor blockers (ARBs) such as valsartan and olmesartan, and calcium channel blockers (CCBs) like amlodipine and azelnidipine. Combination therapy with ARBs and CCBs has shown synergistic effects in reducing vascular injury and microalbuminuria, which may be beneficial for PKD patients.

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Diuretic

Hydrochlorothiazide for Polycystic Kidney Disease (HYDRO-PROTECT Trial)

Q: What is the mechanism of action of this treatment?

Tolvaptan is a vasopressin V2-receptor antagonist that works by inhibiting the action of vasopressin, a hormone that promotes water reabsorption in the kidneys. This inhibition reduces cyst growth and slows the decline in renal function in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Hydrochlorothiazide, a thiazide diuretic, helps manage hypertension and reduces urine volume by decreasing sodium reabsorption in the distal convoluted tubules of the kidneys. For PKD patients, these treatments are crucial as they address both the progression of cyst formation and the management of associated symptoms like hypertension and polyuria, thereby improving overall kidney function and quality of life.

Phase 3

Waitlist Available

Led By Prof. dr. R.T. Gansevoort

Research Sponsored by University Medical Center Groningen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ADPKD diagnosis (modified Ravine criteria)

≥18 years old

Must not have

Orthostatic hypotension complaints or blood pressure <105/65mmHg during screening visit

History of active gout on maintenance preventive treatment for gout (allopurinol, desuric and/or colchicine), defined as ≥2 episodes during the last year

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 168 weeks

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Hydrochlorothiazide may cause dehydration effects like increased urination, dizziness due to low blood pressure, electrolyte imbalances such as low potassium which could affect heart rhythm and muscle function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with ADPKD.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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

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I have had skin cancer before.

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I am currently taking water pills.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 168 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~168 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 168 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Changes in kidney function decline

Secondary study objectives

Change in V2RA discontinuation rate

Change in V2RA dose

Changes in 24-hour urine volume

+11 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: HydrochlorothiazideActive Control1 Intervention

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

Group II: PlaceboPlacebo Group1 Intervention

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

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Tolvaptan is a vasopressin V2-receptor antagonist that works by inhibiting the action of vasopressin, a hormone that promotes water reabsorption in the kidneys. This inhibition reduces cyst growth and slows the decline in renal function in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Hydrochlorothiazide, a thiazide diuretic, helps manage hypertension and reduces urine volume by decreasing sodium reabsorption in the distal convoluted tubules of the kidneys. For PKD patients, these treatments are crucial as they address both the progression of cyst formation and the management of associated symptoms like hypertension and polyuria, thereby improving overall kidney function and quality of life.

A Case Report of Tuberous Sclerosis and Autosomal Dominant Polycystic Kidney Disease in the Era of Tolvaptan.Effectiveness of Tolvaptan in the Treatment for Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-analysis.Tolvaptan: A Review in Autosomal Dominant Polycystic Kidney Disease.