Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease

NCT ID: NCT02160145

Last Updated: 2018-08-08

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1370 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-31

Study Completion Date

2017-04-18

Brief Summary

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The purpose of the study is to determine whether tolvaptan is effective and safe for the treatment of late-stage chronic kidney disease due to autosomal dominant polycystic kidney disease (ADPKD)

Detailed Description

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The protocol will extend the understanding of the efficacy and safety of tolvaptan treatment in ADPKD patients with late stage 2 to early stage 4 CKD (chronic kidney disease).

This trial will compare the efficacy of tolvaptan treatment in reducing the annualized change in estimated glomerular filtration rate (eGFR) from pre-treatment baseline to post-treatment follow-up, as compared with placebo, in subjects who tolerate tolvaptan during an initial run-in period. The change in eGFR, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula, will provide kidney function data that are complementary to the data demonstrating the benefits previously observed primarily in ADPKD subjects with earlier stages of disease.

Also, it will compare the efficacy of tolvaptan treatment in reducing the decline of annualized eGFR slope, as compared with placebo, in this type of subjects. Finally, it will compare the overall and hepatic safety profile of tolvaptan with placebo and to compare incidence of ADPKD complications (outcomes) during the trial

Conditions

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Chronic Kidney Disease Autosomal Dominant Polycystic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Tolvaptan

Tolvaptan (OPC-41061)

Group Type EXPERIMENTAL

Tolvaptan (OPC-41061)

Intervention Type DRUG

Tolvaptan tablets (15 or 30 mg) will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later.

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo tablets will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later

Interventions

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Tolvaptan (OPC-41061)

Tolvaptan tablets (15 or 30 mg) will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later.

Intervention Type DRUG

Placebo

Matching placebo tablets will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male and female subjects with eGFR between 25-65 mL/min/1.73m2 (if aged 18 to55) or eGFR between 25-44 mL/min/1.73m2 (if aged 56 to \<66)
* Tolvaptan naïve
* Diagnosis of ADPKD by modified pei-Ravine criteria 1) 3 cysts per kidney by sonography or 5 cysts by CT or MRI with family history of ADPKD or 2) 10 cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history

Exclusion Criteria

* Women of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of Investigational medicinal product (IMP)
* Women who are breast-feeding and/or who have a positive pregnancy test prior to receiving IMP
* Need for chronic diuretic use
* Hepatic impairment or liver function abnormalities other than that expected for ADPKD with typical cystic liver disease
* Advanced diabetes, evidence of additional significant renal disease, renal cancer, single kidney, recent renal surgery or acute kidney injury
* Contraindications to required trial assessments
* Medical history or medical findings inconsistent with safety or compliance with trial assessments
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Mobile, Alabama, United States

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Phoenix, Arizona, United States

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Tempe, Arizona, United States

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Tucson, Arizona, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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New Haven, Connecticut, United States

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Hudson, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Ocala, Florida, United States

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Port Charlotte, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Meridian, Idaho, United States

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Chicago, Illinois, United States

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Kansas City, Kansas, United States

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Wichita, Kansas, United States

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Baton Rouge, Louisiana, United States

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Lafayette, Louisiana, United States

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Baltimore, Maryland, United States

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Greenbelt, Maryland, United States

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Rockville, Maryland, United States

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Wheaton, Maryland, United States

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Boston, Massachusetts, United States

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Springfield, Massachusetts, United States

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Detroit, Michigan, United States

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Kalamazoo, Michigan, United States

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Pontiac, Michigan, United States

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Roseville, Michigan, United States

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Minneapolis, Minnesota, United States

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Rochester, Minnesota, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Reno, Nevada, United States

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Eatontown, New Jersey, United States

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Voorhees Township, New Jersey, United States

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Buffalo, New York, United States

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Mineola, New York, United States

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New York, New York, United States

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New York, New York, United States

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New York, New York, United States

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Rosedale, New York, United States

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Asheville, North Carolina, United States

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Chapel Hill, North Carolina, United States

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Charlotte, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Fargo, North Dakota, United States

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Grand Forks, North Dakota, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Bethlehem, Pennsylvania, United States

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Doylestown, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Columbia, South Carolina, United States

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Orangeburg, South Carolina, United States

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Knoxville, Tennessee, United States

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Nashville, Tennessee, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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McAllen, Texas, United States

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Burlington, Vermont, United States

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Arlington, Virginia, United States

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Charlottesville, Virginia, United States

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Norfolk, Virginia, United States

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Wenatchee, Washington, United States

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Morgantown, West Virginia, United States

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La Crosse, Wisconsin, United States

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Bahía Blanca, Buenos Aires, Argentina

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Ciudad Autonoma, Buenos Aires, Argentina

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Ciudad Autonoma, Buenos Aires, Argentina

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Ciudad Autonoma, Buenos Aires, Argentina

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Ciudad Autonoma, Buenos Aires, Argentina

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Ciudad Autonoma, Buenos Aires, Argentina

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Junín, Buenos Aires, Argentina

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Pergamino, Buenos Aires, Argentina

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Pilar, Buenos Aires, Argentina

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Sarandí, Buenos Aires, Argentina

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Córdoba, , Argentina

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Córdoba, , Argentina

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Córdoba, , Argentina

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Camperdown, New South Wales, Australia

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Concord, New South Wales, Australia

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New Lambton Heights, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Westmead, New South Wales, Australia

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Woolloongabba, Queensland, Australia

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Adelaide, South Australia, Australia

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Launceston, Tasmania, Australia

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Parkville, Victoria, Australia

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Reservoir, Victoria, Australia

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Richmond, Victoria, Australia

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Perth, Western Australia, Australia

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Aalst, , Belgium

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Antwerp, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Edmonton, Alberta, Canada

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St. John's, Newfoundland and Labrador, Canada

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Scarborough Village, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Brno, , Czechia

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České Budějovice, , Czechia

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Hradec Králové, , Czechia

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Jihlava, , Czechia

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Jilemnice, , Czechia

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Liberec, , Czechia

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Ostrava, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Tábor, , Czechia

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Aalborg, , Denmark

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Aarhus C, , Denmark

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Holstebro, , Denmark

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Odense C, , Denmark

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Viborg, , Denmark

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Brest, Finistere, France

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Bordeaux, Gironde, France

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Toulouse, Haute Garonne, France

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Montpellier, Herault, France

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Grenoble, Isere, France

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Reims, Marne, France

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Vandœuvre-lès-Nancy, Meurthe Et Moselle, France

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Saint-Priest-En-Jarez, Pays de la Loire Region, France

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Lyon, Rhone, France

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Pierre-Bénite, Rhone, France

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Heidelberg, Baden-Wurttemberg, Germany

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Munich, Bavaria, Germany

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Nuremberg, Bavaria, Germany

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Hanover, Lower Saxony, Germany

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Düsseldorf, North Rhine-Westphalia, Germany

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Essen, North Rhine-Westphalia, Germany

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Wiesbaden, North Rhine-Westphalia, Germany

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Dresden, Saxony, Germany

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Budapest, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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Ashkelon, , Israel

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Jerusalem, , Israel

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Nahariya, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Torrette Di Ancona, Ancona, Italy

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Montichiari, Brescia, Italy

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Bari, , Italy

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Bologna, , Italy

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Lecco, , Italy

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Milan, , Italy

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Milan, , Italy

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Modena, , Italy

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Napoli, , Italy

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Pavia, , Italy

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Groningen, , Netherlands

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Nijmegen, , Netherlands

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Bergen, , Norway

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Oslo, , Norway

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Stavanger, , Norway

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Ciechanów, , Poland

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Golub-Dobrzyń, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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San Juan, , Puerto Rico

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Bucharest, , Romania

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Bucharest, , Romania

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Oradea, , Romania

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Krasnoyarsk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Yaroslavl, , Russia

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Pretoria, Gauteng, South Africa

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Durban, KwaZulu-Natal, South Africa

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Cape Town, Western Cape, South Africa

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L'Hospitalet de Llobregat, Barcelona, Spain

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Ciudad Real, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Seville, , Spain

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Seville, , Spain

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Valencia, , Spain

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Gothenburg, , Sweden

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Linköping, , Sweden

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Örebro, , Sweden

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Stockholm, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Exeter, Devon, United Kingdom

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Hull, East Riding Of Yorkshire, United Kingdom

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Brighton, East Sussex, United Kingdom

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London, Greater London, United Kingdom

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Manchester, Greater Manchester, United Kingdom

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Salford, Greater Manchester, United Kingdom

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Stevenage, Hertfordshire, United Kingdom

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Inverness, Highland Region, United Kingdom

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Leicester, Leicestershire, United Kingdom

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Edinburgh, Lothian Region, United Kingdom

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Liverpool, Merseyside, United Kingdom

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Middlesbrough, North Yorkshire, United Kingdom

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Sheffield, South Yorkshire, United Kingdom

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Stoke-on-Trent, Staffordshire, United Kingdom

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Newcastle upon Tyne, Tyne & Wear, United Kingdom

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Coventry, Warwickshire, United Kingdom

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Swansea, , United Kingdom

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Countries

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United States Argentina Australia Belgium Canada Czechia Denmark France Germany Hungary Israel Italy Netherlands Norway Poland Puerto Rico Romania Russia South Africa Spain Sweden United Kingdom

References

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St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

Reference Type DERIVED
PMID: 39356039 (View on PubMed)

Chebib FT, Zhou X, Garbinsky D, Davenport E, Nunna S, Oberdhan D, Fernandes A. Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies. Kidney Med. 2023 Apr 14;5(6):100639. doi: 10.1016/j.xkme.2023.100639. eCollection 2023 Jun.

Reference Type DERIVED
PMID: 37250503 (View on PubMed)

Alpers DH, Lewis JH, Hunt CM, Freston JW, Torres VE, Li H, Wang W, Hoke ME, Roth SE, Westcott-Baker L, Estilo A. Clinical Pattern of Tolvaptan-Associated Liver Injury in Trial Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Pivotal Clinical Trials. Am J Kidney Dis. 2023 Mar;81(3):281-293.e1. doi: 10.1053/j.ajkd.2022.08.012. Epub 2022 Sep 30.

Reference Type DERIVED
PMID: 36191725 (View on PubMed)

Bennett H, McEwan P, Hamilton K, O'Reilly K. Modelling the long-term benefits of tolvaptan therapy on renal function decline in autosomal dominant polycystic kidney disease: an exploratory analysis using the ADPKD outcomes model. BMC Nephrol. 2019 Apr 23;20(1):136. doi: 10.1186/s12882-019-1290-5.

Reference Type DERIVED
PMID: 31014270 (View on PubMed)

Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Koch G, Ouyang J, McQuade RD, Blais JD, Czerwiec FS, Sergeyeva O; REPRISE Trial Investigators. Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease. N Engl J Med. 2017 Nov 16;377(20):1930-1942. doi: 10.1056/NEJMoa1710030. Epub 2017 Nov 4.

Reference Type DERIVED
PMID: 29105594 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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156-13-210

Identifier Type: -

Identifier Source: org_study_id

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