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

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ClinicalTrials.gov Identifier: NCT02065791
Recruitment Status : Active, not recruiting
First Posted : February 19, 2014
Last Update Posted : March 12, 2018
Sponsor:
Collaborator:
The George Institute for Global Health, Australia
Information provided by (Responsible Party):
Janssen Research & Development, LLC

February 17, 2014
February 19, 2014
March 12, 2018
February 17, 2014
June 28, 2019   (Final data collection date for primary outcome measure)
Time to the First Occurrence of an Event in the Primary Composite Endpoint [ Time Frame: Baseline, up to approximately Month 66 ]
The primary composite endpoint of the study includes end-stage kidney disease (ESKD), doubling of serum creatinine, renal or cardiovascular (CV) death.
Time to the First Occurrence of an Event in the Primary Composite Endpoint [ Time Frame: Baseline, up to Month 66 ]
The primary composite endpoint of the study includes end-stage kidney disease (ESKD), doubling of serum creatinine, renal or cardiovascular (CV) death.
Complete list of historical versions of study NCT02065791 on ClinicalTrials.gov Archive Site
  • Time to the First Occurrence of an Event in the Composite Endpoint of CV Death and Hospitalized Congestive Heart Failure [ Time Frame: Baseline, up to approximately Month 66 ]
    The composite endpoint includes CV death and hospitalized congestive heart failure. The CV death is death due to myocardial infarction (MI), stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, presumed sudden CV death, death of unknown cause, or death resulting from a documented CV cause other than those listed above (eg, aneurysm, peripheral vascular disease [PVD]).
  • Time to the First Occurrence of an Event in the Composite Endpoint of CV death, Non-fatal MI, and Non-fatal Stroke (that is, 3-Point Major Adverse Cardiac Event [MACE]) [ Time Frame: Baseline, up to approximately Month 66 ]
    The composite endpoint includes CV death, non-fatal MI, and non-fatal stroke (that is, 3-point MACE).
  • Time to the First Occurrence of Hospitalized Congestive Heart Failure [ Time Frame: Baseline, up to approximately Month 66 ]
    Time to the First Occurrence of Hospitalized Congestive Heart Failure will be assessed.
  • Time to the First Occurrence of an Event in the Renal Composite Endpoint [ Time Frame: Baseline, up to approximately Month 66 ]
    The renal composite endpoint includes ESKD, doubling of serum creatinine, and renal death.
  • Time to CV Death [ Time Frame: Baseline, up to approximately Month 66 ]
    The CV death is death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure related complications, presumed sudden CV death, death of unknown cause, or death resulting from a documented CV cause other than those listed above (for example, aneurysm, PVD).
  • Time to All-cause Death [ Time Frame: Baseline, up to approximately Month 66 ]
    All deaths occurring during the study from any cause.
  • Time to the First Occurrence of an Event in the CV Composite Endpoint [ Time Frame: Baseline, up to approximately Month 66 ]
    The CV composite endpoint includes CV death, non-fatal myocardial infarction (MI), non- fatal stroke, hospitalized congestive heart failure and hospitalized unstable angina.
  • Time to the First Occurrence of an Event in the CV Composite Endpoint [ Time Frame: Baseline, up to Month 66 ]
    The CV composite endpoint includes CV death, non-fatal myocardial infarction (MI), non- fatal stroke, hospitalized congestive heart failure and hospitalized unstable angina.
  • Time to the First Occurrence of an Event in the Renal Composite Endpoint [ Time Frame: Baseline, up to Month 66 ]
    The renal composite endpoint includes ESKD, doubling of serum creatinine, and renal death.
  • Time to All-cause Death [ Time Frame: Baseline, up to Month 66 ]
    All deaths occurring during the study from any cause.
Not Provided
Not Provided
 
Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy
A Randomized, Double-blind, Event-driven, Placebo-controlled, Multicenter Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Nephropathy
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).

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
  • Diabetes Mellitus, Type 2
  • Diabetic Nephropathy
  • Drug: Canagliflozin
    One 100 mg over-encapsulated tablet orally once daily
  • Drug: Placebo
    One matching placebo capsule orally (by mouth) once daily
  • Experimental: Canagliflozin 100 mg
    Each participant will receive 100 mg of canagliflozin once daily
    Intervention: Drug: Canagliflozin
  • Placebo Comparator: Placebo
    Each participant will receive matching placebo once daily
    Intervention: Drug: Placebo
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. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
4401
3627
June 28, 2019
June 28, 2019   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
30 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Czechia,   France,   Germany,   Guatemala,   Hungary,   India,   Japan,   Korea, Republic of,   Lithuania,   Malaysia,   Mexico,   New Zealand,   Philippines,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Serbia,   Slovakia,   South Africa,   Spain,   Taiwan,   Ukraine,   United Arab Emirates,   United Kingdom,   United States
Czech Republic,   Egypt,   Hong Kong
 
NCT02065791
CR103517
2013-004494-28 ( EudraCT Number )
28431754DNE3001 ( Other Identifier: Janssen Research & Development, LLC )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Janssen Research & Development, LLC
Janssen Research & Development, LLC
The George Institute for Global Health, Australia
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Janssen Research & Development, LLC
March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP