Abstract: SA-PO888
Extrapolation of DAPA-CKD Trial End Points in a Broad Urine Albumin Creatinine Ratio Population
Session Information
- CKD: Clinical Trials and Pharmacoepidemiology
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials
Authors
- Davis, Jason, Health Economics and Outcomes Research Ltd, Cardiff, United Kingdom
- Gabb, Peter David, Health Economics and Outcomes Research Ltd, Cardiff, United Kingdom
- Garcia Sanchez, Juan Jose, AstraZeneca PLC, Cambridge, Cambridgeshire, United Kingdom
- Barone, Salvatore, AstraZeneca R&D, Gaithersburg, Maryland, United States
- Ouwens, Johannes Nicolaas Martinus, AstraZeneca, Goteborg, Sweden
- Wheeler, David C., University College London School of Life and Medical Sciences, London, United Kingdom
- L Heerspink, Hiddo Jan, The George Institute for Global Health, Newtown, New South Wales, Australia
Background
The prevalence of chronic kidney disease (CKD) is estimated to be 8-16% worldwide. Patients with CKD have an increased risk of morbidity and mortality. The DAPA-CKD trial (NCT03036150) demonstrated that dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, reduces kidney and cardiovascular (CV) events and mortality in CKD patients with levels of albuminuria in the range 200 to 5000 mg/g. This study aims to extrapolate the dapagliflozin treatment effect in a CKD population with a UACR <200 mg/g.
Methods
The analysis utilised data from the intention-to-treat DAPA-CKD trial population. The primary endpoint and the composite components, sustained estimate glomerular filtration rate (eGFR) decline and end-stage kidney disease (ESKD), were extrapolated as a function of UACR (continuous variable). Annualised estimated event rates spanning a UACR range (0-2,500 mg/g) were generated using poisson models fitted to each endpoint. Event counts were modelled as a function of baseline UACR using the DAPA-CKD data and extended to lower UACR levels. The results were expressed as the ratio of the event rate with dapagliflozin to that with placebo.
Results
The event rate ratios for dapagliflozin versus placebo for the primary composite endpoint (0.67 [95% confidence interval (CI): 0.56-0.80]) and sustained eGFR decline (0.59 [95%CI: 0.48-0.73]) indicated a preserved treatment effect when modelling was applied to those with low UACR (<200 mg/g). There was no evidence to suggest that efficacy would be different in patients with type 2 diabetes mellitus (T2DM) or without T2DM for the primary composite [95% CI: 0.56-0.86 (T2DM) versus 0.39-0.79 (no T2DM)], sustained eGFR decline [95% CI: 0.45-0.73 versus 0.36-0.86] or ESKD [95% CI: 0.55-1.11 versus 0.39-1.26] endpoints.
Conclusion
The analysis suggests that the treatment effect of dapagliflozin might be maintained in relation to the primary endpoint in DAPA-CKD and sustained eGFR decline in patients with low UACR (<200 mg/g). Furthermore, treatment efficacy could be similar between patients with or without T2DM. Validation in a prospective trial is required.
Funding
- Commercial Support –