Trial reportJournal of the American Society of Nephrology : JASN2020
Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS Program.
Trial report in Journal of the American Society of Nephrology : JASN, 2020. The graph read 3 numbers from its abstract, feeding 1 cell of the map, but it casts no vote: it is a later paper about NCT01032629, whose primary report (PMID 28605608) speaks for the trial. It reports registered trial NCT01032629. Cited by 10 papers, 3 of them syntheses that pooled it.
What it found
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Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions.
Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions.
Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions.
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SGLT2 inhibitors×kidney outcomes
No readable resultOpen on the map →What to test next →13 readable studies in this cell: 10 favour the treatment, 1 find no difference, 2 favour the comparator.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ-28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus
Open the trial in the graphA Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects With Type 2 Diabetes Mellitus
Open the trial in the graphWho cites it
10 citing papers in PubMed, 3 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.The Cochrane database of systematic reviews · 2024Pooled it
- Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.Lancet (London, England) · 2022Pooled it
- SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.Frontiers in public health · 2021Pooled it
- Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial.Clinical journal of the American Society of Nephrology : CJASN · 2021Trial
- Real-World Associations of KidneyIntelX Risk Stratification With Guideline-Directed Therapy, Kidney Outcomes, and Metabolic Trajectories in Early Diabetic Kidney Disease.Diabetes, obesity & metabolism · 2026Article
- Mitochondrial DNA copy number is associated with incident chronic kidney disease and proteinuria in the AIDS linked to the intravenous experience cohort.Scientific reports · 2023Article
- Canagliflozin Attenuates PromarkerD Diabetic Kidney Disease Risk Prediction Scores.Journal of clinical medicine · 2023Article
- SGLT2 Inhibition in Type 1 Diabetes with Diabetic Kidney Disease: Potential Cardiorenal Benefits Can Outweigh Preventable Risk of Diabetic Ketoacidosis.Current diabetes reports · 2022Review
- Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022Article
- Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials.EClinicalMedicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
backgroundTraditionally, clinical trials evaluating effects of a new therapy with creatinine-based renal end points use doubling of serum creatinine (equivalent to a 57% eGFR reduction), requiring large sample sizes.
methodsTo assess whether eGFR declines <57% could detect canagliflozin's effects on renal outcomes, we conducted a
resultsAmong the 10,142 participants, 93 (0.9%), 161 (1.6%), 352 (3.5%), and 800 (7.9%) participants recorded renal outcomes on the basis of 57%, 50%, 40%, or 30% eGFR reduction, respectively, during a mean follow-up of 188 weeks. Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions. In analyses that controlled for the acute hemodynamic fall in eGFR, effect sizes were comparable, regardless of whether a 57%, 50%, 40%, or 30% eGFR reduction was used. Estimated sample sizes for studies on the basis of lesser eGFR reductions were much reduced by controlling for this early hemodynamic effect.
conclusionsDeclines in eGFR <57% may provide robust estimates of canagliflozin's effects on renal outcomes if the analysis controls for the drug's acute hemodynamic effect. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629 and CANVAS-R, NCT01989754.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.