Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy

NCT ID: NCT02065791

Last Updated: 2019-12-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

4401 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-17

Study Completion Date

2018-10-30

Brief Summary

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The goal of this study is to assess whether canagliflozin has a renal and vascular protective effect in reducing the progression of renal impairment relative to placebo in participants with type 2 diabetes mellitus (T2DM), Stage 2 or 3 chronic kidney disease (CKD) and macroalbuminuria, who are receiving standard of care including a maximum tolerated labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).

Detailed Description

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This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled (an inactive substance that is compared with a medication to test whether the medication has a real effect), parallel-group, multicenter study of the effects of canagliflozin on renal and cardiovascular outcomes in participants with type 2 diabetes mellitus (T2DM) and diabetic nephropathy, who are receiving standard of care including a maximum tolerated daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).

The study will consist of a pretreatment phase (several weeks), and a double-blind treatment phase (up to approximately 66 months). During the pretreatment phase all participants will also receive diet/exercise counseling for lipid and blood pressure management as well as counseling on renal and cardiovascular (CV) risk factor medication. A post-treatment follow-up contact or visit will take place approximately 30 days after the last dose of study drug or the completion of the study. The total duration of the study is estimated to be about 5 to 5.5 years. Approximately 4,200 participants will be randomized in a 1:1 ratio to canagliflozin or matching placebo. Participants randomized to canagliflozin will receive a dose of 100 mg once daily. The overall safety and tolerability of canagliflozin will be evaluated by collecting information on adverse events, laboratory tests, vital signs (pulse, blood pressure), physical examination, and body weight.

Conditions

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Diabetes Mellitus, Type 2 Diabetic Nephropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Canagliflozin 100 mg

Each participant will receive 100 mg of canagliflozin once daily

Group Type EXPERIMENTAL

Canagliflozin

Intervention Type DRUG

One 100 mg over-encapsulated tablet orally once daily

Placebo

Each participant will receive matching placebo once daily

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

One matching placebo capsule orally (by mouth) once daily

Interventions

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Canagliflozin

One 100 mg over-encapsulated tablet orally once daily

Intervention Type DRUG

Placebo

One matching placebo capsule orally (by mouth) once daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Type 2 diabetes mellitus with a hemoglobin A1c (HbA1c) greater than or equal to (\>=) 6.5 percent (%) and less than or equal to (\<=) 12.0%, with an estimated glomerular filtration rate (eGFR) of \>= 30 milliliter (mL)/minute (min)/1.73meter (m)\^2 and less than (\<) 90 mL/min/1.73 m\^2
* Participants need to be on a stable maximum tolerated labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for at least 4 weeks prior to randomization
* Must have a urine albumin to creatinine ratio (UACR) of greater than (\>) 300 milligram (mg)/gram (g) and \<= 5000 mg/g

Exclusion Criteria

* History of diabetic ketoacidosis or type 1 diabetes mellitus
* History of hereditary glucose-galactose malabsorption or primary renal glucosuria
* Renal disease that required treatment with immunosuppressive therapy
* Known significant liver disease
* Current or history of New York Heart Association (NYHA) Class IV heart failure
* Blood potassium level \>5.5 millimole (mmol)/liter (L) during Screening
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The George Institute for Global Health, Australia

OTHER

Sponsor Role collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Birmingham, Alabama, United States

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Montgomery, Alabama, United States

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Tempe, Arizona, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Sherwood, Arkansas, United States

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Bakersfield, California, United States

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Chula Vista, California, United States

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Covina, California, United States

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Downey, California, United States

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Fountain Valley, California, United States

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Hawthorne, California, United States

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Inglewood, California, United States

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Laguna Hills, California, United States

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Lakewood, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Lynwood, California, United States

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Northridge, California, United States

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Oakland, California, United States

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Orange, California, United States

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Pasadena, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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Salinas, California, United States

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San Diego, California, United States

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San Dimas, California, United States

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Stanford, California, United States

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Tustin, California, United States

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Whittier, California, United States

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Denver, Colorado, United States

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Golden, Colorado, United States

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Lakewood, Colorado, United States

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Washington, Colorado, United States

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Washington D.C., District of Columbia, United States

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Coral Springs, Florida, United States

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Doral, Florida, United States

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Hialeah, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Miami Springs, Florida, United States

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North Miami Beach, Florida, United States

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Ocala, Florida, United States

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Port Charlotte, Florida, United States

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St. Petersburg, Florida, United States

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Winter Park, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Columbus, Georgia, United States

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Roswell, Georgia, United States

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Snellville, Georgia, United States

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Stockbridge, Georgia, United States

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Chicago, Illinois, United States

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Crystal Lake, Illinois, United States

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Gurnee, Illinois, United States

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Mount Prospect, Illinois, United States

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Winfield, Illinois, United States

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Fort Wayne, Indiana, United States

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Indianapolis, Indiana, United States

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Merrillville, Indiana, United States

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Michigan City, Indiana, United States

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Muncie, Indiana, United States

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Council Bluffs, Iowa, United States

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Louisville, Kentucky, United States

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Paducah, Kentucky, United States

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Kenner, Louisiana, United States

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Rockport, Maine, United States

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Scarborough, Maine, United States

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Annapolis, Maryland, United States

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Baltimore, Maryland, United States

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Beltsville, Maryland, United States

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Hyattsville, Maryland, United States

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Silver Spring, Maryland, United States

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Boston, Massachusetts, United States

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Plymouth, Massachusetts, United States

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Springfield, Massachusetts, United States

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Worcester, Massachusetts, United States

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Flint, Michigan, United States

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Jackson, Mississippi, United States

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Chesterfield, Missouri, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Fremont, Nebraska, United States

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Lincoln, Nebraska, United States

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Omaha, Nebraska, United States

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Reno, Nebraska, United States

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Las Vegas, Nevada, United States

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Eatontown, New Jersey, United States

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Albuquerque, New Mexico, United States

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Albany, New York, United States

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Binghamton, New York, United States

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Buffalo, New York, United States

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Great Neck, New York, United States

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Lake Success, New York, United States

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New Hyde Park, New York, United States

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New York, New York, United States

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Ridgewood, New York, United States

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Riverhead, New York, United States

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Smithtown, New York, United States

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Springfield Gardens, New York, United States

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Asheville, North Carolina, United States

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Calabash, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Greensboro, North Carolina, United States

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Greenville, North Carolina, United States

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High Point, North Carolina, United States

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Morehead City, North Carolina, United States

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Morganton, North Carolina, United States

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Raleigh, North Carolina, United States

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Tabor City, North Carolina, United States

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Whiteville, North Carolina, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Maumee, Ohio, United States

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Roseburg, Oregon, United States

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Beaver, Pennsylvania, United States

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Bethlehem, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Anderson, South Carolina, United States

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Columbia, South Carolina, United States

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Lancaster, South Carolina, United States

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Murrells Inlet, South Carolina, United States

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Orangeburg, South Carolina, United States

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Sumter, South Carolina, United States

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Chattanooga, Tennessee, United States

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Knoxville, Tennessee, United States

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Memphis, Tennessee, United States

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Arlington, Texas, United States

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Corpus Christi, Texas, United States

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Corsicana, Texas, United States

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Dallas, Texas, United States

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Edinburg, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Mesquite, Texas, United States

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San Antonio, Texas, United States

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Schertz, Texas, United States

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Sugar Land, Texas, United States

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Temple, Texas, United States

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Waco, Texas, United States

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Salt Lake City, Utah, United States

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Bennington, Vermont, United States

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Burlington, Vermont, United States

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Bluefield, Virginia, United States

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Mechanicsville, Virginia, United States

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Norfolk, Virginia, United States

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Suffolk, Virginia, United States

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Spokane, Washington, United States

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Huntington, West Virginia, United States

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Milwaukee, Wisconsin, United States

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Bahía Blanca, , Argentina

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Buenos Aires, , Argentina

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Ciudad Autonoma Buenos Aires, , Argentina

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Corrientes, , Argentina

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Córdoba, , Argentina

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Godoy Cruz, , Argentina

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Junín, , Argentina

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La Plata, , Argentina

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La Plata Lpl Lpl, , Argentina

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Mar del Plata, , Argentina

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Mendoza, , Argentina

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Morón, , Argentina

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Munro, , Argentina

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Paraná, , Argentina

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Quilmes, , Argentina

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Ramos Mejía, , Argentina

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Rosario, , Argentina

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Salta, , Argentina

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San Luis, , Argentina

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San Martín, , Argentina

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San Migeul de Tucuman, , Argentina

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San Miguel de Tucumán, , Argentina

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San Nicolás, , Argentina

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Santa Fe, , Argentina

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Sarandí, , Argentina

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Tapiales, , Argentina

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Temperley, , Argentina

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Villa María, , Argentina

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Zarate, Buenos Aires, , Argentina

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Cairns, , Australia

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Concord, , Australia

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Darlinghurst, , Australia

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Elizabeth Vale, , Australia

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Fremantle, , Australia

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Gosford, , Australia

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Heidelberg, , Australia

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Keswick, , Australia

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Meadowbrook, , Australia

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Parkville, , Australia

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Reservoir, , Australia

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Richmond, , Australia

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St Albans, , Australia

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St Leonards, , Australia

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Sydney, , Australia

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Woolloongabba, , Australia

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Aparecida de Goiânia, , Brazil

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Belém, , Brazil

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Belo Horizonte, , Brazil

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Botucatu, , Brazil

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Brasília, , Brazil

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Campina Grande do Sul, , Brazil

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Campinas, , Brazil

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Canoas, , Brazil

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Caxias do Sul, , Brazil

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Curitiba, , Brazil

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Fortaleza, , Brazil

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Joinville, , Brazil

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Juiz de Fora, , Brazil

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Maringá, , Brazil

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Passo Fundo, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Santo André, , Brazil

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São José do Rio Preto, , Brazil

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São José dos Campos, , Brazil

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São Paulo, , Brazil

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Tatuí, , Brazil

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Blagoevgrad, , Bulgaria

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Byala, , Bulgaria

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Golenci, , Bulgaria

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Pazardzhik, , Bulgaria

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Edmonton, Alberta, Canada

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New Westminster, British Columbia, Canada

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Vancouver, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Brampton, Ontario, Canada

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London, Ontario, Canada

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Newmarket, Ontario, Canada

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Oshawa, Ontario, Canada

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Smiths Falls, Ontario, Canada

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Thornhill, Ontario, Canada

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Toronto, Ontario, Canada

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Weston, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Québec, , Canada

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Toronto, , Canada

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Vancouver, , Canada

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Concepción, , Chile

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Santiago, , Chile

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Temuco, , Chile

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Beijing, , China

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Changchun, , China

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Changde, , China

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Changsha, , China

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Chengdu, , China

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Chenzhou, , China

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Dalian, , China

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Foshan, , China

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Guangzhou, , China

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Huai'an, , China

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Nanchang, , China

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Nanjing, , China

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Shanghai, , China

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Shenyang, , China

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Ürümqi, , China

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Wuhan, , China

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Xi'an, , China

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Barranquilla, , Colombia

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Bogotá, , Colombia

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Bucaramanga, , Colombia

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Cali, , Colombia

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Floridablanca, , Colombia

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Manizales, , Colombia

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Medellín, , Colombia

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Pasto, , Colombia

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Pereira, , Colombia

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Choceň, , Czechia

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České Budějovice, , Czechia

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Český Krumlov, , Czechia

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Havlíčkův Brod, , Czechia

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Hradec Kralove-Vekose, , Czechia

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Hradec nad Svitavou, , Czechia

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Jindřichův Hradec, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Slaný, , Czechia

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Trutnov, , Czechia

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Uherské Hradiště, , Czechia

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Ústí nad Labem, , Czechia

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Besançon, , France

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Brest, , France

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Colmar, , France

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Corbeil-Essonnes, , France

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Créteil, , France

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Grenoble, , France

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Lyon, , France

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Marseille, , France

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Metz, , France

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Nantes, , France

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Paris, , France

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Pierre-Bénit, , France

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Poitiers, , France

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Saint-Priest-en-Jarez, , France

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Strasbourg, , France

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Toulouse, , France

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Bad Kreuznach - Bosenheim, , Germany

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Cologne, , Germany

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Dietzenbach, , Germany

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Dresden, , Germany

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Essen, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Münster, , Germany

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Guatemala City, , Guatemala

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Baja, , Hungary

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Balatonfüred, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Eger, , Hungary

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Esztergom, , Hungary

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Gödöllő, , Hungary

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Gyula, , Hungary

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Hu-4012 Debrecen N/a, , Hungary

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Kaposvár, , Hungary

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Kecskemét, , Hungary

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Komárom, , Hungary

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Nyíregyháza, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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Szigetvár, , Hungary

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Veszprém, , Hungary

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Zalaegerszeg, , Hungary

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Calicut, , India

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Chennai, , India

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Delhi, , India

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Hyderabad, , India

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Kozhikode, , India

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Lucknow, , India

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Ludhiyāna, , India

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Mangalore, , India

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Mumbai, , India

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Mysore, , India

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Secunderabad, , India

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Trivandrum, , India

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Vijayawada, , India

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Visakhapatnam, , India

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Ageo-shi, , Japan

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Chiyoda-ku, , Japan

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Fukuoka, , Japan

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Hamamatsu, , Japan

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Hamura-shi, , Japan

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Ina-shi, , Japan

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Izumisano, , Japan

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Kamakura-shi, , Japan

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Kanazawa, , Japan

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Kawanishi-shi, , Japan

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Koriyama-shi, , Japan

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Kuki-shi, , Japan

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Kyoto, , Japan

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Matsuyama, , Japan

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Midori, , Japan

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Minatoku, , Japan

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Nagoya, , Japan

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Osaka, , Japan

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Ota-shi, , Japan

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Saiki-shi, , Japan

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Sashima-gun, , Japan

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Shinjuku-ku, , Japan

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Toyama, , Japan

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Uwajima-shi, , Japan

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Yamanashi, , Japan

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Yokohama, , Japan

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Kaunas, , Lithuania

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Klaipėda, , Lithuania

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Šiauliai, , Lithuania

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Batu Caves, , Malaysia

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Ipoh, , Malaysia

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Johor Bahru, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuantan, , Malaysia

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Malacca, , Malaysia

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Perai, , Malaysia

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Petaling Jaya, , Malaysia

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Seremban, , Malaysia

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Seri Manjung, , Malaysia

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Sungai Petani, Kedah, , Malaysia

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Tampin, , Malaysia

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Temerluh, , Malaysia

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Aguascalientes, , Mexico

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Celaya, , Mexico

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Chihuahua City, , Mexico

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Ciudad de Mexic, , Mexico

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Cuautitlán Izcalli, , Mexico

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Culiacán, , Mexico

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Durango, , Mexico

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El Salto, , Mexico

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Guadalajara, , Mexico

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León, , Mexico

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Mexico City, , Mexico

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Mérida, , Mexico

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México, , Mexico

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Monterrey, , Mexico

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Morelia, , Mexico

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Orizaba, , Mexico

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Pachuca, , Mexico

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Querétaro, , Mexico

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San Luis Potosí City, , Mexico

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Tlalnepantla, , Mexico

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Veracruz, , Mexico

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Zapopan, , Mexico

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Dunedin, , New Zealand

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Palmerston North, , New Zealand

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Rotorua, , New Zealand

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Takapuna Auckland, , New Zealand

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Tauranga, , New Zealand

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Wellington, , New Zealand

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Cagayan de Oro, , Philippines

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Cebu, , Philippines

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Cebuu City, , Philippines

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Davao City, , Philippines

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Iloilo City, , Philippines

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Lipa City, , Philippines

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Marikina City, , Philippines

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Pasay, , Philippines

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Pasig, , Philippines

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Quezon City, , Philippines

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San Fernando City, , Philippines

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Tagbilaran City, , Philippines

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Taytay, , Philippines

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Bydgoszcz, , Poland

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Chorzów, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Parczew, , Poland

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Poznan, , Poland

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Radom, , Poland

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Rzeszów, , Poland

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Torun, , Poland

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Warswa, , Poland

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Wroclaw, , Poland

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Zgierz, , Poland

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Żnin, , Poland

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Caguas, , Puerto Rico

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Ponce, , Puerto Rico

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San Juan, , Puerto Rico

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Brasov, , Romania

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Deva, , Romania

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Iași, , Romania

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Oradea, , Romania

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Ploieşti, , Romania

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Târgu Mureş, , Romania

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Timișoara, , Romania

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Arkhangelsk, , Russia

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Barnaul, , Russia

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Ivanovo, , Russia

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Kemerovo, , Russia

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Moscow, , Russia

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Novosibirsk, , Russia

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Petrozavodsk, , Russia

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Rostov-on-Don, , Russia

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Ryazan, , Russia

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Saint Petersburg, , Russia

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Saratov, , Russia

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Sestroretsk, Saint-Petersburg, , Russia

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Tomsk, , Russia

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Ufa, , Russia

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Volgograd, , Russia

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Yaroslavl, , Russia

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Belgrade, , Serbia

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Niš, , Serbia

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Zaječar, , Serbia

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Bardejov, , Slovakia

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Bratislava, , Slovakia

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Košice, , Slovakia

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Ľubochňa, , Slovakia

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Nitra, , Slovakia

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Prievidza, , Slovakia

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Púchov, , Slovakia

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Rimavská Sobota, , Slovakia

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Svidník, , Slovakia

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Štúrovo, , Slovakia

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Žilina, , Slovakia

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Cape Town, , South Africa

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Durban, , South Africa

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Isipingo Rail, , South Africa

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Johannesburg, , South Africa

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Krugersdorp, , South Africa

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Port Elizabeth, , South Africa

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Pretoria, , South Africa

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Pretoria Gauteng, , South Africa

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Soweto, , South Africa

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Busan, , South Korea

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Daegu, , South Korea

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Incheon, , South Korea

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Seongnam, , South Korea

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Seoul, , South Korea

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A Coruña, , Spain

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Almería, , Spain

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Barcelona, , Spain

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Burela de Cabo, , Spain

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Ciudad Real, , Spain

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Getafe, , Spain

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Girona, , Spain

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Granada, , Spain

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La Roca del Vallès, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Málaga, , Spain

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Palma de Mallorca, , Spain

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Pozuelo de Alarcón, , Spain

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Sagunto, , Spain

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Santander, , Spain

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Seville, , Spain

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Valencia, , Spain

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Vic, , Spain

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Viladecans, , Spain

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Kaohsiung City, , Taiwan

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New Taipei City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Chernivtsi, , Ukraine

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Dnipropetrovsk, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kiev, , Ukraine

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Kyiv, , Ukraine

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Ternopil, , Ukraine

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Vinnitsya, , Ukraine

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Vinnytsia, , Ukraine

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Zaporizhzhia, , Ukraine

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Ajman, , United Arab Emirates

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Dubai, , United Arab Emirates

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Sharjah city, , United Arab Emirates

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Aberdeen, , United Kingdom

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Antrim, , United Kingdom

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Barry, , United Kingdom

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Birmingham, , United Kingdom

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Blackburn, , United Kingdom

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Bolton, , United Kingdom

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Bournemouth, , United Kingdom

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Bradford, , United Kingdom

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Bristol, , United Kingdom

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Burbage, , United Kingdom

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Cardff, , United Kingdom

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Cardiff, , United Kingdom

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Carlshalton, , United Kingdom

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Carmarthen, , United Kingdom

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Chester, , United Kingdom

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Darlington, , United Kingdom

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Doncaster, , United Kingdom

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Durham, , United Kingdom

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Ely, , United Kingdom

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Hampstead, , United Kingdom

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Harlow, , United Kingdom

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Huntingdon, , United Kingdom

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Liskeard, , United Kingdom

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London, , United Kingdom

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Middlesbrough, , United Kingdom

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Plymouth, , United Kingdom

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Rhyl, , United Kingdom

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Royal Leamington Spa, , United Kingdom

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Rugby, , United Kingdom

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Salford, , United Kingdom

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Stoke-on-Trent, , United Kingdom

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Swansea, , United Kingdom

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Torpoint, , United Kingdom

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Watford, , United Kingdom

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Welwyn Garden City, , United Kingdom

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Westcliff-on-Sea, , United Kingdom

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Wokingham, , United Kingdom

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Wolverhampton, , United Kingdom

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Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Australia Brazil Bulgaria Canada Chile China Colombia Czechia France Germany Guatemala Hungary India Japan Lithuania Malaysia Mexico New Zealand Philippines Poland Puerto Rico Romania Russia Serbia Slovakia South Africa South Korea Spain Taiwan Ukraine United Arab Emirates United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Bayes-Genis A, Cai A, Liu Y, Pandey A, Pop-Busui R, Hansen M, Januzzi JL. Impact of canagliflozin on heart stress and outcomes: Pooled insights from CREDENCE and CANVAS. Eur J Heart Fail. 2025 Jul 21. doi: 10.1002/ejhf.3786. Online ahead of print.

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PMID: 40689549 (View on PubMed)

Oshima M, Buizen L, Jongs N, Levin A, Chertow GM, Wheeler DC, Heerspink HJL, Arnott C, Jardine MJ, Mahaffey KW, Pollock C, Herrington WG, Perkovic V, Neuen BL. Sodium-Glucose Cotransporter 2 Inhibition and Hospitalizations in Patients with CKD: A Meta-Analysis of Kidney Outcome Trials. Clin J Am Soc Nephrol. 2025 Jul 14;20(9):1206-1214. doi: 10.2215/CJN.0000000771.

Reference Type DERIVED
PMID: 40658498 (View on PubMed)

Jongs N, Gasparyan SB, Frison L, Schloemer P, Brinker M, Little DJ, Heerspink HJL. Use of eGFR Slope Thresholds as End Point Components in a Kidney Disease Progression Hierarchical Composite End Point. J Am Soc Nephrol. 2025 Jun 17. doi: 10.1681/ASN.0000000766. Online ahead of print. No abstract available.

Reference Type DERIVED
PMID: 40526444 (View on PubMed)

Januzzi JLJ, Sattar N, Vaduganathan M, Magaret CA, Rhyne RF, Liu Y, Masson S, Butler J, Hansen MK. A validated multivariable machine learning model to predict cardio-kidney risk in diabetic kidney disease. Cardiovasc Diabetol. 2025 May 15;24(1):213. doi: 10.1186/s12933-025-02779-5.

Reference Type DERIVED
PMID: 40375260 (View on PubMed)

Doi Y, Hamano T, Yamaguchi O, Isaka Y. Canagliflozin may increase thromboembolic events in males with erythrocytosis but not in females. Blood Adv. 2025 Jul 8;9(13):3202-3212. doi: 10.1182/bloodadvances.2025016320.

Reference Type DERIVED
PMID: 40239057 (View on PubMed)

Nguyen TN, Yu J, Perkovic V, Jardine M, Mahaffey KW, Chow CK, Arnott C, Lindley RI. The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials. J Am Geriatr Soc. 2025 Jun;73(6):1787-1796. doi: 10.1111/jgs.19444. Epub 2025 Mar 19.

Reference Type DERIVED
PMID: 40105285 (View on PubMed)

Chatur S, Vaduganathan M, Fletcher RA, Perkovic V, Heerspink H, Arnott C, Pollock C, Mahaffey KW, Neal B, Jardine M, Solomon SD, Neuen BL. Canagliflozin reduces oral loop diuretic intensification in patients with type 2 diabetes: A participant-level pooled analysis of the CANVAS and CREDENCE trials. Eur J Heart Fail. 2025 Jun;27(6):994-1002. doi: 10.1002/ejhf.3586. Epub 2025 Jan 23.

Reference Type DERIVED
PMID: 39844714 (View on PubMed)

Vaduganathan M, Cannon CP, Jardine MJ, Heerspink HJL, Arnott C, Neuen BL, Sarraju A, Gogate J, Seufert J, Neal B, Perkovic V, Mahaffey KW, Kosiborod MN. Effects of canagliflozin on total heart failure events across the kidney function spectrum: Participant-level pooled analysis from the CANVAS Program and CREDENCE trial. Eur J Heart Fail. 2024 Sep;26(9):1967-1975. doi: 10.1002/ejhf.3292. Epub 2024 Jun 26.

Reference Type DERIVED
PMID: 38932575 (View on PubMed)

Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

Reference Type DERIVED
PMID: 38770818 (View on PubMed)

Januzzi JL Jr, Liu Y, Sattar N, Yavin Y, Pollock CA, Butler J, Jardine M, Heerspink HJL, Masson S, Breyer M, Hansen MK. Vascular endothelial growth factors and risk of cardio-renal events: Results from the CREDENCE trial. Am Heart J. 2024 May;271:38-47. doi: 10.1016/j.ahj.2024.02.016. Epub 2024 Feb 22.

Reference Type DERIVED
PMID: 38401646 (View on PubMed)

Sharma A, Razaghizad A, Joury A, Levin A, Bajaj HS, Mancini GBJ, Wong NC, Slee A, Ang FG, Rapattoni W, Neuen BL, Arnott C, Perkovic V, Mahaffey KW. Primary and Secondary Cardiovascular and Kidney Prevention With Canagliflozin: Insights From the CANVAS Program and CREDENCE Trial. J Am Heart Assoc. 2024 Feb 6;13(3):e031586. doi: 10.1161/JAHA.123.031586. Epub 2024 Jan 19.

Reference Type DERIVED
PMID: 38240199 (View on PubMed)

Mohebi R, Liu Y, Hansen MK, Yavin Y, Sattar N, Pollock CA, Butler J, Jardine M, Masson S, Heerspink HJL, Januzzi JL Jr. Associations of Angiopoietin 2 and Vascular Endothelial Growth Factor-A Concentrations with Clinical End Points. Clin J Am Soc Nephrol. 2024 Apr 1;19(4):429-437. doi: 10.2215/CJN.0000000000000389. Epub 2023 Dec 14.

Reference Type DERIVED
PMID: 38099944 (View on PubMed)

Fletcher RA, Jongs N, Chertow GM, McMurray JJV, Arnott C, Jardine MJ, Mahaffey KW, Perkovic V, Rockenschaub P, Rossing P, Correa-Rotter R, Toto RD, Vaduganathan M, Wheeler DC, Heerspink HJL, Neuen BL. Effect of SGLT2 Inhibitors on Discontinuation of Renin-angiotensin System Blockade: A Joint Analysis of the CREDENCE and DAPA-CKD Trials. J Am Soc Nephrol. 2023 Dec 1;34(12):1965-1975. doi: 10.1681/ASN.0000000000000248. Epub 2023 Oct 25.

Reference Type DERIVED
PMID: 37876229 (View on PubMed)

Heerspink HJL, Jongs N, Schloemer P, Little DJ, Brinker M, Tasto C, Karpefors M, Wheeler DC, Bakris G, Perkovic V, Nkulikiyinka R, Rossert J, Gasparyan SB. Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression. J Am Soc Nephrol. 2023 Dec 1;34(12):2025-2038. doi: 10.1681/ASN.0000000000000243. Epub 2023 Oct 24.

Reference Type DERIVED
PMID: 37872654 (View on PubMed)

Yu J, Sweeting AN, Gianacas C, Houston L, Lee V, Fletcher RA, Perkovic V, Li Q, Neuen BL, Berwanger O, Heerspink HJL, de Zeeuw D, Arnott C. The effects of canagliflozin in type 2 diabetes in subgroups defined by population-specific body mass index: Insights from the CANVAS Program and CREDENCE trial. Diabetes Obes Metab. 2023 Dec;25(12):3724-3735. doi: 10.1111/dom.15267. Epub 2023 Sep 6.

Reference Type DERIVED
PMID: 37671609 (View on PubMed)

Januzzi JL, Mohebi R, Liu Y, Sattar N, Heerspink HJL, Tefera E, Vaduganathan M, Butler J, Yavin Y, Li J, Pollock CA, Perkovic V, Neal B, Hansen MK. Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial. Circulation. 2023 Aug 22;148(8):651-660. doi: 10.1161/CIRCULATIONAHA.123.065251. Epub 2023 Aug 21.

Reference Type DERIVED
PMID: 37603600 (View on PubMed)

Mohebi R, Liu Y, Hansen MK, Yavin Y, Sattar N, Pollock CA, Butler J, Jardine M, Masson S, Heerspink HJL, Januzzi JL Jr. Insulin growth factor axis and cardio-renal risk in diabetic kidney disease: an analysis from the CREDENCE trial. Cardiovasc Diabetol. 2023 Jul 12;22(1):176. doi: 10.1186/s12933-023-01916-2.

Reference Type DERIVED
PMID: 37438734 (View on PubMed)

Fletcher RA, Arnott C, Rockenschaub P, Schutte AE, Carpenter L, Vaduganathan M, Agarwal R, Bakris G, Chang TI, Heerspink HJL, Jardine MJ, Mahaffey KW, Neal B, Pollock C, Jun M, Rodgers A, Perkovic V, Neuen BL. Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials. J Am Heart Assoc. 2023 Jul 4;12(13):e028516. doi: 10.1161/JAHA.122.028516. Epub 2023 Jun 22.

Reference Type DERIVED
PMID: 37345834 (View on PubMed)

Ferrannini G, Pollock C, Natali A, Yavin Y, Mahaffey KW, Ferrannini E. Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE. Cardiovasc Diabetol. 2023 Apr 29;22(1):100. doi: 10.1186/s12933-023-01832-5.

Reference Type DERIVED
PMID: 37120538 (View on PubMed)

van der Hoek S, Jongs N, Oshima M, Neuen BL, Stevens J, Perkovic V, Levin A, Mahaffey KW, Pollock C, Greene T, Wheeler DC, Jardine MJ, Heerspink HJL. Glycemic Control and Effects of Canagliflozin in Reducing Albuminuria and eGFR: A Post Hoc Analysis of the CREDENCE Trial. Clin J Am Soc Nephrol. 2023 Jun 1;18(6):748-758. doi: 10.2215/CJN.0000000000000161. Epub 2023 Mar 31.

Reference Type DERIVED
PMID: 36999981 (View on PubMed)

Yi TW, Smyth B, Di Tanna GL, Arnott C, Cardoza K, Kang A, Pollock C, Agarwal R, Bakris G, Charytan DM, de Zeeuw D, Heerspink HJL, Neal B, Wheeler DC, Cannon CP, Zhang H, Zinman B, Perkovic V, Levin A, Mahaffey KW, Jardine M; CREDENCE Trial Investigators. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial. Am J Kidney Dis. 2023 Jul;82(1):84-96.e1. doi: 10.1053/j.ajkd.2022.12.015. Epub 2023 Mar 7.

Reference Type DERIVED
PMID: 36889425 (View on PubMed)

Sarraju A, Bakris G, Cannon CP, Cherney D, Damaraju CV, Figtree GA, Gogate J, Greene T, Heerspink HJL, Januzzi JL Jr, Neal B, Jardine MJ, Blais J, Kosiborod M, Levin A, Lingvay I, Weir MR, Perkovic V, Mahaffey KW. Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria. J Am Coll Cardiol. 2022 Nov 1;80(18):1721-1731. doi: 10.1016/j.jacc.2022.08.772.

Reference Type DERIVED
PMID: 36302584 (View on PubMed)

Nunes JC, Yu J, Arnott C, Jardine MJ, Perkovic V, Mahaffey KW. Canagliflozin, mental health adverse events and diabetes: Exploratory analysis of the CREDENCE trial and CANVAS Program. Diabetes Obes Metab. 2022 Dec;24(12):2459-2464. doi: 10.1111/dom.14832. Epub 2022 Aug 19. No abstract available.

Reference Type DERIVED
PMID: 35938182 (View on PubMed)

Li JW, Arnott C, Heerspink HJL, MBiostat QL, Cannon CP, Wheeler DC, Charytan DM, Barraclough J, Figtree GA, Agarwal R, Bakris G, de Zeeuw D, Greene T, Levin A, Pollock C, Zhang H, Zinman B, Mahaffey KW, Perkovic V, Neal B, Jardine MJ. Effect of Canagliflozin on Total Cardiovascular Burden in Patients With Diabetes and Chronic Kidney Disease: A Post Hoc Analysis From the CREDENCE Trial. J Am Heart Assoc. 2022 Aug 16;11(16):e025045. doi: 10.1161/JAHA.121.025045. Epub 2022 Aug 5.

Reference Type DERIVED
PMID: 35929472 (View on PubMed)

Charytan DM, Yu J, Jardine MJ, Cannon CP, Agarwal R, Bakris G, Greene T, Levin A, Pollock C, Powe NR, Arnott C, Mahaffey KW; CREDENCE study investigators. Potential Effects of Elimination of the Black Race Coefficient in eGFR Calculations in the CREDENCE Trial. Clin J Am Soc Nephrol. 2022 Mar;17(3):361-373. doi: 10.2215/CJN.08980621. Epub 2022 Jan 21.

Reference Type DERIVED
PMID: 35063969 (View on PubMed)

Heerspink HJL, Oshima M, Zhang H, Li J, Agarwal R, Capuano G, Charytan DM, Craig J, de Zeeuw D, Di Tanna GL, Levin A, Neal B, Perkovic V, Wheeler DC, Yavin Y, Jardine MJ. Canagliflozin and Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial. Am J Kidney Dis. 2022 Feb;79(2):244-256.e1. doi: 10.1053/j.ajkd.2021.05.005. Epub 2021 May 23.

Reference Type DERIVED
PMID: 34029680 (View on PubMed)

Zhou Z, Jardine MJ, Li Q, Neuen BL, Cannon CP, de Zeeuw D, Edwards R, Levin A, Mahaffey KW, Perkovic V, Neal B, Lindley RI; CREDENCE Trial Investigators*. Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis. Stroke. 2021 May;52(5):1545-1556. doi: 10.1161/STROKEAHA.120.031623. Epub 2021 Apr 20.

Reference Type DERIVED
PMID: 33874750 (View on PubMed)

Yu J, Li J, Leaver PJ, Arnott C, Huffman MD, Udell JA, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Matthews DR, Shaw W, Rosenthal N, Neal B, Figtree GA. Effects of canagliflozin on myocardial infarction: a post hoc analysis of the CANVAS programme and CREDENCE trial. Cardiovasc Res. 2022 Mar 16;118(4):1103-1114. doi: 10.1093/cvr/cvab128.

Reference Type DERIVED
PMID: 33826709 (View on PubMed)

Jardine M, Zhou Z, Lambers Heerspink HJ, Hockham C, Li Q, Agarwal R, Bakris GL, Cannon CP, Charytan DM, Greene T, Levin A, Li JW, Neuen BL, Neal B, Oh R, Oshima M, Pollock C, Wheeler DC, de Zeeuw D, Zhang H, Zinman B, Mahaffey KW, Perkovic V. Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria: A CREDENCE Secondary Analysis. Clin J Am Soc Nephrol. 2021 Mar 8;16(3):384-395. doi: 10.2215/CJN.15260920. Epub 2021 Feb 22.

Reference Type DERIVED
PMID: 33619120 (View on PubMed)

Ye N, Jardine MJ, Oshima M, Hockham C, Heerspink HJL, Agarwal R, Bakris G, Schutte AE, Arnott C, Chang TI, Gorriz JL, Cannon CP, Charytan DM, de Zeeuw D, Levin A, Mahaffey KW, Neal B, Pollock C, Wheeler DC, Luca Di Tanna G, Cheng H, Perkovic V, Neuen BL. Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial. Circulation. 2021 May 4;143(18):1735-1749. doi: 10.1161/CIRCULATIONAHA.120.048740. Epub 2021 Feb 8.

Reference Type DERIVED
PMID: 33554616 (View on PubMed)

Sarraju A, Li J, Cannon CP, Chang TI, Agarwal R, Bakris G, Charytan DM, de Zeeuw D, Greene T, Heerspink HJL, Levin A, Neal B, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Perkovic V, Jardine M, Mahaffey KW. Effects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure: Results from the CREDENCE trial. Am Heart J. 2021 Mar;233:141-148. doi: 10.1016/j.ahj.2020.12.008. Epub 2020 Dec 22.

Reference Type DERIVED
PMID: 33358942 (View on PubMed)

Durkin M, Blais J. Linear Projection of Estimated Glomerular Filtration Rate Decline with Canagliflozin and Implications for Dialysis Utilization and Cost in Diabetic Nephropathy. Diabetes Ther. 2021 Feb;12(2):499-508. doi: 10.1007/s13300-020-00953-4. Epub 2020 Dec 18.

Reference Type DERIVED
PMID: 33340064 (View on PubMed)

Willis M, Nilsson A, Kellerborg K, Ball P, Roe R, Traina S, Beale R, Newell I. Cost-Effectiveness of Canagliflozin Added to Standard of Care for Treating Diabetic Kidney Disease (DKD) in Patients with Type 2 Diabetes Mellitus (T2DM) in England: Estimates Using the CREDEM-DKD Model. Diabetes Ther. 2021 Jan;12(1):313-328. doi: 10.1007/s13300-020-00968-x. Epub 2020 Dec 2.

Reference Type DERIVED
PMID: 33263893 (View on PubMed)

Willis M, Asseburg C, Slee A, Nilsson A, Neslusan C. Development and Internal Validation of a Discrete Event Simulation Model of Diabetic Kidney Disease Using CREDENCE Trial Data. Diabetes Ther. 2020 Nov;11(11):2657-2676. doi: 10.1007/s13300-020-00923-w. Epub 2020 Sep 15.

Reference Type DERIVED
PMID: 32930969 (View on PubMed)

Jardine MJ, Zhou Z, Mahaffey KW, Oshima M, Agarwal R, Bakris G, Bajaj HS, Bull S, Cannon CP, Charytan DM, de Zeeuw D, Di Tanna GL, Greene T, Heerspink HJL, Levin A, Neal B, Pollock C, Qiu R, Sun T, Wheeler DC, Zhang H, Zinman B, Rosenthal N, Perkovic V; CREDENCE Study Investigators. Renal, Cardiovascular, and Safety Outcomes of Canagliflozin by Baseline Kidney Function: A Secondary Analysis of the CREDENCE Randomized Trial. J Am Soc Nephrol. 2020 May;31(5):1128-1139. doi: 10.1681/ASN.2019111168.

Reference Type DERIVED
PMID: 32354987 (View on PubMed)

Cannon CP, Perkovic V, Agarwal R, Baldassarre J, Bakris G, Charytan DM, de Zeeuw D, Edwards R, Greene T, Heerspink HJL, Jardine MJ, Levin A, Li JW, Neal B, Pollock C, Wheeler DC, Zhang H, Zinman B, Mahaffey KW. Evaluating the Effects of Canagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease According to Baseline HbA1c, Including Those With HbA1c <7%: Results From the CREDENCE Trial. Circulation. 2020 Feb 4;141(5):407-410. doi: 10.1161/CIRCULATIONAHA.119.044359. Epub 2019 Nov 11. No abstract available.

Reference Type DERIVED
PMID: 31707795 (View on PubMed)

Mahaffey KW, Jardine MJ, Bompoint S, Cannon CP, Neal B, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Capuano G, de Zeeuw D, Greene T, Levin A, Pollock C, Sun T, Wheeler DC, Yavin Y, Zhang H, Zinman B, Rosenthal N, Brenner BM, Perkovic V. Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups. Circulation. 2019 Aug 27;140(9):739-750. doi: 10.1161/CIRCULATIONAHA.119.042007. Epub 2019 Jul 11.

Reference Type DERIVED
PMID: 31291786 (View on PubMed)

Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW; CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 Jun 13;380(24):2295-2306. doi: 10.1056/NEJMoa1811744. Epub 2019 Apr 14.

Reference Type DERIVED
PMID: 30990260 (View on PubMed)

Jardine MJ, Mahaffey KW, Neal B, Agarwal R, Bakris GL, Brenner BM, Bull S, Cannon CP, Charytan DM, de Zeeuw D, Edwards R, Greene T, Heerspink HJL, Levin A, Pollock C, Wheeler DC, Xie J, Zhang H, Zinman B, Desai M, Perkovic V; CREDENCE study investigators. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics. Am J Nephrol. 2017 Dec 13;46(6):462-472. doi: 10.1159/000484633. Online ahead of print.

Reference Type DERIVED
PMID: 29253846 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2013-004494-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

28431754DNE3001

Identifier Type: OTHER

Identifier Source: secondary_id

CR103517

Identifier Type: -

Identifier Source: org_study_id

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