drugset / Trial / NCT01032629
CANVAS - CANagliflozin cardioVascular Assessment Study
Phase 3
Completed
4330 enrolled
Janssen Research & Development, LLC
The George Institute for Global Health, Australia · collab
RandomizedParallel-groupQuadruple-blindTreatment
Summary
The study will assess canagliflozin (JNJ-28431754) in the treatment of patients with type 2 diabetes mellitus (T2DM) with regard to cardiovascular (CV) risk for major adverse cardiac events (MACE). Other objectives include evaluating the overall safety, tolerability, and effectiveness of canagliflozin. The data from this study will be combined with the data from CANVAS-R study (Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects with T2DM, NCT01989754) in a pre-specified integrated analysis of CV safety outcomes to satisfy US FDA post-marketing requirements for canagliflozin.
Timeline
- Start
- 2009-12-09
- Primary completion
- 2017-02-22
- Completion
- 2017-02-22
Outcome
Results reported · no primary-endpoint met/missed verdict (typical of a dose-finding / safety study)
registry Placebo vs Canagliflozin (Total); p = 0.1120; Hazard Ratio (HR) 0.88 (95% CI 0.75 to 1.03) NCT01032629 ↗
Publications
- Moedt E, Koshino A, Jongs N, Ju W, Nair V, Kretzler M, Hansen MK, Arnott CG, Wheeler DC, Rossing P, Coca SG, Hammarstedt A, Greasley PJ, Bjornstad P, Bakker SJL, Heerspink HJL. Association of Urinary EGF with Kidney Outcomes and Effects of Sodium-Glucose Cotransporter 2 Inhibition. J Am Soc Nephrol. 2026 Apr 2. doi: 10.1681/ASN.0000001086. Online ahead of print.
- Heerspink HJL, Collier WH, Chaudhari J, Miao S, Tighiouart H, Appel GB, Caravaca-Fontan F, Floege J, Hannedouche T, Imai E, Jafar TH, Lewis JB, Li PKT, Locatelli F, Maes BD, Neuen BL, Perkovic V, Perrone RD, Remuzzi G, Schena FP, Wanner C, Greene T, Inker LA. A meta-analysis of albuminuria as a surrogate endpoint for kidney failure. Nat Med. 2026 Jan;32(1):281-287. doi: 10.1038/s41591-025-04057-z. Epub 2025 Nov 6.
- Mottl A, Scott C, Green JB, Heerspink HJL, Mann JFE, McGill JB, Nangaku M, Rosenstock J, Rossing P, Li L, Li N, Vaduganathan M, Agarwal R; CONFIDENCE Trial Investigators. Baseline Kidney Function, Albuminuria, and Urine Albumin-Creatinine Ratio Reduction with Finerenone, Empagliflozin, or Both: Post Hoc Analyses of CONFIDENCE Trial. J Am Soc Nephrol. 2026 Apr 1;37(4):764-776. doi: 10.1681/ASN.0000000928. Epub 2025 Nov 6.
- 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 Dec;27(12):2887-2896. doi: 10.1002/ejhf.3786. Epub 2025 Jul 21.
- 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.
- 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.
- 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.
- Rasmussen DGK, Hansen MK, Frederiksen P, Luo Y, Pehrsson M, Neal B, Karsdal MA, Genovese F. Association of type III collagen turnover with cardiovascular outcomes and impact with canagliflozin in the CANVAS Program: A post hoc analysis. Diabetes Obes Metab. 2024 Sep;26(9):4060-4068. doi: 10.1111/dom.15761. Epub 2024 Jul 16.
- 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.
- Tangri N, Ferguson TW, Bamforth RJ, Leon SJ, Arnott C, Mahaffey KW, Kotwal S, Heerspink HJL, Perkovic V, Fletcher RA, Neuen BL. Machine learning for prediction of chronic kidney disease progression: Validation of the Klinrisk model in the CANVAS Program and CREDENCE trial. Diabetes Obes Metab. 2024 Aug;26(8):3371-3380. doi: 10.1111/dom.15678. Epub 2024 May 28.
- 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.
- 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.
- 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.
- Sen T, Ju W, Nair V, Ladd P, Menon R, Otto EA, Pyle L, Vigers T, Nelson RG, Arnott C, Neal B, Hansen MK, Kretzler M, Bjornstad P, Heerspink HJL. Sodium glucose co-transporter 2 inhibition increases epidermal growth factor expression and improves outcomes in patients with type 2 diabetes. Kidney Int. 2023 Oct;104(4):828-839. doi: 10.1016/j.kint.2023.07.007. Epub 2023 Aug 4.
- 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.
- Borisov AN, Kutz A, Christ ER, Heim MH, Ebrahimi F. Canagliflozin and Metabolic Associated Fatty Liver Disease in Patients With Diabetes Mellitus: New Insights From CANVAS. J Clin Endocrinol Metab. 2023 Oct 18;108(11):2940-2949. doi: 10.1210/clinem/dgad249.
- 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.
- Rasmussen DGK, Hansen MK, Blair J, Jatkoe TA, Neal B, Karsdal MA, Genovese F. Endotrophin is a risk marker of complications in CANagliflozin cardioVascular Assessment Study (CANVAS): a randomized controlled trial. Cardiovasc Diabetol. 2022 Nov 28;21(1):261. doi: 10.1186/s12933-022-01666-7.
- 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.
- Ferrannini E, Baldi S, Scozzaro T, Tsimihodimos V, Tesfaye F, Shaw W, Rosenthal N, Figtree GA, Neal B, Mahaffey KW, Perkovic V, Hansen MK. Fasting Substrate Concentrations Predict Cardiovascular Outcomes in the CANagliflozin cardioVascular Assessment Study (CANVAS). Diabetes Care. 2022 Aug 1;45(8):1893-1899. doi: 10.2337/dc21-2398.
- Vaduganathan M, Sattar N, Xu J, Butler J, Mahaffey KW, Neal B, Shaw W, Rosenthal N, Pfeifer M, Hansen MK, Januzzi JL Jr. Stress Cardiac Biomarkers, Cardiovascular and Renal Outcomes, and Response to Canagliflozin. J Am Coll Cardiol. 2022 Feb 8;79(5):432-444. doi: 10.1016/j.jacc.2021.11.027.
- Waijer SW, Sen T, Arnott C, Neal B, Kosterink JGW, Mahaffey KW, Parikh CR, de Zeeuw D, Perkovic V, Neuen BL, Coca SG, Hansen MK, Gansevoort RT, Heerspink HJL. Association between TNF Receptors and KIM-1 with Kidney Outcomes in Early-Stage Diabetic Kidney Disease. Clin J Am Soc Nephrol. 2022 Feb;17(2):251-259. doi: 10.2215/CJN.08780621. Epub 2021 Dec 7.
- Young TK, Li JW, Kang A, Heerspink HJL, Hockham C, Arnott C, Neuen BL, Zoungas S, Mahaffey KW, Perkovic V, de Zeeuw D, Fulcher G, Neal B, Jardine M. Effects of canagliflozin compared with placebo on major adverse cardiovascular and kidney events in patient groups with different baseline levels of HbA1c, disease duration and treatment intensity: results from the CANVAS Program. Diabetologia. 2021 Nov;64(11):2402-2414. doi: 10.1007/s00125-021-05524-1. Epub 2021 Aug 26.
- 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.
- Yu J, Arnott C, Neuen BL, Heersprink HL, Mahaffey KW, Cannon CP, Khan SS, Baldridge AS, Shah SJ, Huang Y, Li C, Figtree GA, Perkovic V, Jardine MJ, Neal B, Huffman MD. Cardiovascular and renal outcomes with canagliflozin according to baseline diuretic use: a post hoc analysis from the CANVAS Program. ESC Heart Fail. 2021 Apr;8(2):1482-1493. doi: 10.1002/ehf2.13236. Epub 2021 Feb 17.
- Januzzi JL Jr, Butler J, Sattar N, Xu J, Shaw W, Rosenthal N, Pfeifer M, Mahaffey KW, Neal B, Hansen MK. Insulin-Like Growth Factor Binding Protein 7 Predicts Renal and Cardiovascular Outcomes in the Canagliflozin Cardiovascular Assessment Study. Diabetes Care. 2021 Jan;44(1):210-216. doi: 10.2337/dc20-1889. Epub 2020 Nov 6.
- Januzzi JL Jr, Xu J, Li J, Shaw W, Oh R, Pfeifer M, Butler J, Sattar N, Mahaffey KW, Neal B, Hansen MK. Effects of Canagliflozin on Amino-Terminal Pro-B-Type Natriuretic Peptide: Implications for Cardiovascular Risk Reduction. J Am Coll Cardiol. 2020 Nov 3;76(18):2076-2085. doi: 10.1016/j.jacc.2020.09.004.
- Neuen BL, Ohkuma T, Neal B, Matthews DR, de Zeeuw D, Mahaffey KW, Fulcher G, Blais J, Li Q, Jardine MJ, Perkovic V, Wheeler DC. Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. Am J Kidney Dis. 2021 Jan;77(1):23-34.e1. doi: 10.1053/j.ajkd.2020.06.018. Epub 2020 Sep 21.
- Oshima M, Neal B, Toyama T, Ohkuma T, Li Q, de Zeeuw D, Heerspink HJL, Mahaffey KW, Fulcher G, Canovatchel W, Matthews DR, Perkovic V. Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS Program. J Am Soc Nephrol. 2020 Oct;31(10):2446-2456. doi: 10.1681/ASN.2019121312. Epub 2020 Jul 21.
- Matthews DR, Wysham C, Davies M, Slee A, Alba M, Lee M, Perkovic V, Mahaffey KW, Neal B. Effects of canagliflozin on initiation of insulin and other antihyperglycaemic agents in the CANVAS Program. Diabetes Obes Metab. 2020 Nov;22(11):2199-2203. doi: 10.1111/dom.14143. Epub 2020 Aug 24.
- Zhou Z, Jardine M, Perkovic V, Matthews DR, Mahaffey KW, de Zeeuw D, Fulcher G, Desai M, Oh R, Simpson R, Watts NB, Neal B. Canagliflozin and fracture risk in individuals with type 2 diabetes: results from the CANVAS Program. Diabetologia. 2019 Oct;62(10):1854-1867. doi: 10.1007/s00125-019-4955-5. Epub 2019 Aug 10.
- Figtree GA, Radholm K, Barrett TD, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Matthews DR, Shaw W, Neal B. Effects of Canagliflozin on Heart Failure Outcomes Associated With Preserved and Reduced Ejection Fraction in Type 2 Diabetes Mellitus. Circulation. 2019 May 28;139(22):2591-2593. doi: 10.1161/CIRCULATIONAHA.119.040057. Epub 2019 Mar 17. No abstract available.
- Zhou Z, Lindley RI, Radholm K, Jenkins B, Watson J, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Shaw W, Oh R, Desai M, Matthews DR, Neal B. Canagliflozin and Stroke in Type 2 Diabetes Mellitus. Stroke. 2019 Feb;50(2):396-404. doi: 10.1161/STROKEAHA.118.023009.
- Neuen BL, Ohkuma T, Neal B, Matthews DR, de Zeeuw D, Mahaffey KW, Fulcher G, Desai M, Li Q, Deng H, Rosenthal N, Jardine MJ, Bakris G, Perkovic V. Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function. Circulation. 2018 Oct 9;138(15):1537-1550. doi: 10.1161/CIRCULATIONAHA.118.035901.
- Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Erondu N, Shaw W, Barrett TD, Weidner-Wells M, Deng H, Matthews DR, Neal B. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol. 2018 Sep;6(9):691-704. doi: 10.1016/S2213-8587(18)30141-4. Epub 2018 Jun 21.
- Wittbrodt ET, Eudicone JM, Bell KF, Enhoffer DM, Latham K, Green JB. Eligibility varies among the 4 sodium-glucose cotransporter-2 inhibitor cardiovascular outcomes trials: implications for the general type 2 diabetes US population. Am J Manag Care. 2018 Apr;24(8 Suppl):S138-S145.
- Radholm K, Figtree G, Perkovic V, Solomon SD, Mahaffey KW, de Zeeuw D, Fulcher G, Barrett TD, Shaw W, Desai M, Matthews DR, Neal B. Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program. Circulation. 2018 Jul 31;138(5):458-468. doi: 10.1161/CIRCULATIONAHA.118.034222.
- Mahaffey KW, Neal B, Perkovic V, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Fabbrini E, Sun T, Li Q, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin for Primary and Secondary Prevention of Cardiovascular Events: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study). Circulation. 2018 Jan 23;137(4):323-334. doi: 10.1161/CIRCULATIONAHA.117.032038. Epub 2017 Nov 13.
- Yale JF, Xie J, Sherman SE, Garceau C. Canagliflozin in Conjunction With Sulfonylurea Maintains Glycemic Control and Weight Loss Over 52 Weeks: A Randomized, Controlled Trial in Patients With Type 2 Diabetes Mellitus. Clin Ther. 2017 Nov;39(11):2230-2242.e2. doi: 10.1016/j.clinthera.2017.10.003. Epub 2017 Nov 3.
- Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12.
- Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2016 Jan;101(1):157-66. doi: 10.1210/jc.2015-3167. Epub 2015 Nov 18.
- Gavin JR 3rd, Davies MJ, Davies M, Vijapurkar U, Alba M, Meininger G. The efficacy and safety of canagliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2015;31(9):1693-702. doi: 10.1185/03007995.2015.1067192. Epub 2015 Sep 4.
- Fulcher G, Matthews DR, Perkovic V, de Zeeuw D, Mahaffey KW, Weiss R, Rosenstock J, Capuano G, Desai M, Shaw W, Vercruysse F, Meininger G, Neal B. Efficacy and Safety of Canagliflozin Used in Conjunction with Sulfonylurea in Patients with Type 2 Diabetes Mellitus: A Randomized, Controlled Trial. Diabetes Ther. 2015 Sep;6(3):289-302. doi: 10.1007/s13300-015-0117-z. Epub 2015 Jun 17.
- Neal B, Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Ways K, Desai M, Shaw W, Capuano G, Alba M, Jiang J, Vercruysse F, Meininger G, Matthews D; CANVAS Trial Collaborative Group. Efficacy and safety of canagliflozin, an inhibitor of sodium-glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes. Diabetes Care. 2015 Mar;38(3):403-11. doi: 10.2337/dc14-1237. Epub 2014 Dec 2.
- Weir MR, Kline I, Xie J, Edwards R, Usiskin K. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR). Curr Med Res Opin. 2014 Sep;30(9):1759-68. doi: 10.1185/03007995.2014.919907. Epub 2014 May 22.
- Nyirjesy P, Sobel JD, Fung A, Mayer C, Capuano G, Ways K, Usiskin K. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin. 2014 Jun;30(6):1109-19. doi: 10.1185/03007995.2014.890925. Epub 2014 Feb 21.
- Neal B, Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Stein P, Desai M, Shaw W, Jiang J, Vercruysse F, Meininger G, Matthews D. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)--a randomized placebo-controlled trial. Am Heart J. 2013 Aug;166(2):217-223.e11. doi: 10.1016/j.ahj.2013.05.007. Epub 2013 Jun 24.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | CANAGLIFLOZIN ANHYDROUS | Small molecule | 100 mg | Oral |
| Subject | CANAGLIFLOZIN ANHYDROUS | Small molecule | 300 mg | Oral |