HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life

ADPKD Clinical Trial

— HYDRO-PROTECT  

Official title:

HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05373264
• Other study ID #: 202100714
• Secondary ID: 2021-005612-61
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 2024
• Est. completion date: July 2029

Study information

• Verified date: September 2023
• Source: University Medical Center Groningen
• Contact: Dr. E Meijer
• Phone: +31 50 3616161
• Email: esther.meijer[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: July 2029
• Est. primary completion date: July 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• ADPKD
• Kidney Diseases
• Polycystic Kidney Diseases

Intervention

Drug:
• Hydrochlorothiazide 25 mg
An oral capsule containing 25mg of hydrochlorothiazide
• Placebo
A matching oral capsule containing placebo

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussel
Belgium	University Hospital Leuven	Leuven
France	Hospital La Cavale Blanche	Brest
France	Necker-Enfants Malades Hospital	Paris
Germany	Charité University Hospital	Berlin
Germany	Med. Klinik und Poliklinik III, Universitätsklinikum Dresden.	Dresden
Germany	University Hospital Cologne	Köln
Netherlands	Amsterdam University Medical Center	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Erasmus University Medical Center	Rotterdam
Spain	Fundación Puigvert	Barcelona
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	University of Sheffield Medical School	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in kidney function decline	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 all available creatinine values from week 12 until end of treatment between the tolvaptan/placebo and tolvaptan/HCT group.	156 weeks
Secondary	Changes in eGFR from baseline compared to end of study (12 weeks after End of Treatment)	A secondary outcome is the change in eGFR from baseline compared to end of study (12 weeks after end of treatment)	168 weeks
Secondary	Incidence of 30% decrease in eGFR, end stage kidney disease (EKSD) or renal death	A secondary outcome is the incidence of a 30% decrease in eGFR, occurrence of end stage kidney disease (EKSD) or renal death during the entire study period (until the end of study (12 weeks after end of treatment)	168 weeks
Secondary	Changes in 24-hour urine volume	A secondary outcome is the change in 24-hour urine volume, measured at baseline, week 12, week 48, week 96 and week 156 (end of treatment)	156 weeks
Secondary	Quality of life, assessed by the TIPS questionnaire	Changes in Quality of Life measured by the Tolvaptan Impact of Polyuria Scale questionnaire (TIPS) at baseline, week 12, week 48, week 96 and week 156 (end of treatment)	156 weeks
Secondary	Quality of life, assessed by the ADPKD-UIS questionnaire	Changes in Quality of Life measured by the ADPKD-Urinary Impact Scale questionnaire (ADPKD-UIS) at baseline, week 12, week 48, week 96 and week 156 (end of treatment)	156 weeks
Secondary	Quality of life, assessed by the SF-12 questionnaire	Changes in Quality of Life measured by the Short Form 12 questionnaire (SF-12) at baseline, week 12, week 48, week 96 and week 156 (end of treatment)	156 weeks
Secondary	Quality of life, assessed by the EQ-5D questionnaire	Changes in Quality of Life measured by the EuroQol-5 Dimension questionnaire (EQ-5D) at baseline, week 12, week 48, week 96 and week 156 (end of treatment)	156 weeks
Secondary	Change in V2RA dose	V2RA dose during each study visit and compared at the end of study visit (12 weeks after end of treatment) between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group	168 weeks
Secondary	Change in V2RA discontinuation rate	The V2RA discontinuation rate will be compared at the end of study visit (12 weeks after end of treatment) between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group	168 weeks
Secondary	Changes in serum sodium concentration	Changes in serum sodium concentration between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group, measured from baseline until the end of study (12 weeks after end of treatment)	168 weeks
Secondary	Changes in serum potassium concentration	Changes in serum potassium concentration between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group, measured from baseline until the end of study (12 weeks after end of treatment)	168 weeks
Secondary	Changes in plasma serum calcium concentration	Changes in plasma serum calcium concentration between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group, measured from baseline until the end of study (12 weeks after end of treatment)	168 weeks
Secondary	Changes in serum phosphate concentration	Changes in serum phosphate concentration between tolvaptan/placebo and tolvaptan/hydrochlorothiazide group, measured from baseline until the end of study (12 weeks after end of treatment)	168 weeks
Secondary	Incidence of (serious) adverse events	Incidence of (serious) adverse events from baseline until the end of study (12 weeks after end of treatment)	168 weeks