HYDROchlorothiazide to PROTECT polycystic kidney disease patients and improve their quality of life (HYDRO-PROTECT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Medical Center Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

28 Jun 2024 → ongoing

Decision date (initial)

2026-04-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Otsuka Global (company that produces tolvaptan) · ZonMw (The Netherlands Organisation for Health Research and Development

External identifiers

EU CT number

2022-500210-26-00

WHO UTN

U1111-1283-3529

ClinicalTrials.gov

NCT05373264

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Autosomal Dominant Polycystic Kidney Disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective treatment for ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a small scale clinical study, addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-hour urinary volume and potentially increased renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in ADPKD patients. The primary study outcome is the rate of kidney function decline (expressed as eGFR slope, in mL/min/1.73m2 per year) in HCT versus placebo treated patients, calculated by linear mixed model analysis using all available creatinine values from week 12 until end of treatment.

Secondary objectives 1

1. Secondary endpoints are related to kidney function, quality of life, tolerability and safety. They include the following: 1) changes in eGFR between baseline and EoS (off treatment) 2) incidence of a 30% decrease in eGFR, end stage kidney disease or death from renal causes 3) quality of life 4) changes in quality of life related questionnaire scores (TIPS, ADPKD-UIS, EQ-5D-5L and SF-12) 5) changes in 24-hour urine volume 6) tolvaptan dose and discontinuation rate 7) changes in serum electrolytes (potassium, sodium, calcium and phosphate) and 8) changes in blood pressure

Conditions and MedDRA coding

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1) ADPKD diagnosis (modified Ravine criteria) 2 ≥18 years old 3) eGFR > 25 mL/min/1.73m2 (in Belgium eGFR > 35 mL/min/1.73m2) 4) On stable treatment with the highest tolerated dose of V2RA for a minimum of 3 months

Exclusion criteria 1

1. 1) Known intolerance to hydrochlorothiazide 2) Use of any diuretic 3) Changes in antihypertensive treatment in the last month 4) Orthostatic hypotension or blood pressure < 105/65 mmHg 5) Uncontrolled hypertension (blood pressure >160/100mmHg) 6) Hypokalemia (<3.5 mmol/L) 7) Diabetes mellitus type 1 or type 2 8) Primary renal disease other than ADPKD 9) History of active gout despite maintenance preventive treatment for gout (allopurinol, desuric, febuxostat and/or colchicine), defined as ≥2 episodes during the last year 10) History of skin cancer (basal cell, squamous cell and melanoma) 11) Anuria 12) Severe liver function impairment 13) Hypercalcemia 14) Salt losing nephropathy 15) Pregnancy 16) Breast feeding 17) Concurrent use of any medications listed under 8.1.2 18) Not able to give informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The rate of kidney function decline (expressed as eGFR slope, in mL/min/1.73m2 per year), as calculated by linear mixed model analysis, using all available creatinine values from week 12 until week 156 (EoT) for HCT- versus placebo-treated patients.

Secondary endpoints 1

1. 1) changes in eGFR between baseline and EoS (off treatment) 2) incidence of a 30% decrease in eGFR, end stage kidney disease or death from renal causes 3) changes in quality of life related questionnaire scores (TIPS, ADPKD-UIS, EQ-5D-5L and SF-12) 4) changes in 24-hour urine volume 5) tolvaptan dose and discontinuation rate 6) changes in serum electrolytes (potassium, sodium, calcium and phosphate) 7) changes in blood pressure

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Medical Center Groningen

Sponsor organisation

University Medical Center Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

University Medical Center Groningen

Contact name

R.T. Gansevoort

Public contact point

Organisation

University Medical Center Groningen

Contact name

R.T. Gansevoort

Locations

6 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications