HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life (HYDRO-PROTECT)

University Medical Center Groningen (UMCG)

Status and phase: Not yet enrolling; Phase 3

Conditions: ADPKD

Treatments: Drug: Hydrochlorothiazide 25 mg; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05373264

202100714

2021-005612-61 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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)

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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300 participants in 2 patient groups, including a placebo group

Hydrochlorothiazide

Active Comparator group

Description:

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

Treatment:

Drug: Hydrochlorothiazide 25 mg

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo