Clinical trial NCT05373264: HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
Official title: HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: ADPKD
Keywords: ADPKD
Tolvaptan
Hydrochlorothiazide
Quality of Life
Side effects
Polyuria
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2022-05-13
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An investigator driven, multicenter, placebo-controlled, randomized clinical trial.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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)

Eligibility criteria: 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)

Primary outcomes:
measure: Changes in kidney function decline
timeFrame: 156 weeks
Secondary outcomes:
measure: Changes in eGFR from baseline compared to end of study (12 weeks after End of Treatment)
timeFrame: 168 weeks
measure: Incidence of 30% decrease in eGFR, end stage kidney disease (EKSD) or renal death
timeFrame: 168 weeks
measure: Changes in 24-hour urine volume
timeFrame: 156 weeks
measure: Quality of life, assessed by the TIPS questionnaire
timeFrame: 156 weeks
measure: Quality of life, assessed by the ADPKD-UIS questionnaire
timeFrame: 156 weeks
measure: Quality of life, assessed by the SF-12 questionnaire
timeFrame: 156 weeks
measure: Quality of life, assessed by the EQ-5D questionnaire
timeFrame: 156 weeks
measure: Change in V2RA dose
timeFrame: 168 weeks
measure: Change in V2RA discontinuation rate
timeFrame: 168 weeks
measure: Changes in serum sodium concentration
timeFrame: 168 weeks
measure: Changes in serum potassium concentration
timeFrame: 168 weeks
measure: Changes in plasma serum calcium concentration
timeFrame: 168 weeks
measure: Changes in serum phosphate concentration
timeFrame: 168 weeks
measure: Incidence of (serious) adverse events
timeFrame: 168 weeks
Other outcomes:
Locations:
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Brest
country: France
facility: Hospital La Cavale Blanche
city: Paris
country: France
facility: Necker-Enfants Malades Hospital
city: Berlin
country: Germany
facility: Charité University Hospital
city: Dresden
country: Germany
facility: Med. Klinik und Poliklinik III, Universitätsklinikum Dresden.
city: Köln
country: Germany
facility: University Hospital Cologne
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
city: Barcelona
country: Spain
facility: Fundación Puigvert
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Sheffield
country: United Kingdom
facility: University of Sheffield Medical School
Study officials:
affiliation: University Medical Center Groningen
name: Prof. dr. R.T. Gansevoort
role: PRINCIPAL_INVESTIGATOR
References: