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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-005612-61 | EudraCT Number |
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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.
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)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hydrochlorothiazide | Active Comparator | Oral hydrochlorothiazide 25mg, once daily, for a total of 156 weeks |
|
| Placebo | Placebo Comparator | Matching oral placebo, once daily, for a total of 156 weeks. The placebo is inert. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydrochlorothiazide 25 mg | Drug | An oral capsule containing 25mg of hydrochlorothiazide |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Incidence of 30% decrease in eGFR, end stage kidney disease (EKSD) or renal death |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Dr. E Meijer | Contact | +31 50 3616161 | esther.meijer@umcg.nl | |
| T. Bais, MD | Contact | t.bais@umcg.nl |
| Name | Affiliation | Role |
|---|---|---|
| Prof. dr. R.T. Gansevoort | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cliniques Universitaires Saint-Luc | Recruiting | Brussels | Belgium |
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An investigator driven, multicenter, placebo-controlled, randomized clinical trial.
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| Placebo | Drug | A matching oral capsule containing placebo |
|
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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| University Hospital Leuven | Recruiting | Leuven | Belgium |
|
| Hospital La Cavale Blanche | Recruiting | Brest | France |
|
| Necker-Enfants Malades Hospital | Recruiting | Paris | France |
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| Charité University Hospital | Recruiting | Berlin | Germany |
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| University Hospital Cologne | Recruiting | Cologne | Germany |
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| Med. Klinik und Poliklinik III, Universitätsklinikum Dresden. | Recruiting | Dresden | Germany |
|
| Amsterdam University Medical Center | Recruiting | Amsterdam | Netherlands |
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| University Medical Center Groningen | Recruiting | Groningen | Netherlands |
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| Erasmus University Medical Center | Recruiting | Rotterdam | Netherlands |
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| Fundación Puigvert | Recruiting | Barcelona | Spain |
|
| La Fundación Jiménez Díaz | Recruiting | Madrid | Spain |
|
| ID | Term |
|---|---|
| D016891 | Polycystic Kidney, Autosomal Dominant |
| D011141 | Polyuria |
| ID | Term |
|---|---|
| D007690 | Polycystic Kidney Diseases |
| D052177 | Kidney Diseases, Cystic |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000072661 | Ciliopathies |
| D030342 | Genetic Diseases, Inborn |
| D014555 | Urination Disorders |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D006852 | Hydrochlorothiazide |
| ID | Term |
|---|---|
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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