Cardiovascular Safety and Efficacy of Vadadust for the Treatment of Anemia in Non-Dialysis Dependent CKD: Design and Baseline Characteristics. American heart journal Chertow, G. M., Pergola, P. E., Agarwal, R., Block, G. A., Farag, Y. M., Jardine, A. G., Koury, M. J., Luo, W., Khawaja, Z., Lewis, E. F., Matsushita, K., McCullough, P. A., Parfrey, P. S., Wittes, J., Walters, K. A., Tseng, C., Lin, T., Sarnak, M. J., Vargo, D. L., Winkelmayer, W. C., Eckardt, K. 2020


Current clinical practice guidelines for anemia management in non-dialysis dependent chronic kidney disease (NDD-CKD) recommend the use of erythropoiesis-stimulating agents (ESAs) as standard of care. Vadadustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates endogenous erythropoietin production. The PRO2TECT program comprises two global, Phase 3, randomized, open-label, active-controlled, sponsor-blind clinical trials to evaluate safety and efficacy of vadadustat vs darbepoetin alfa in adult patients with anemia associated with NDD-CKD. Patients recruited into the ESA-untreated NDD-CKD trial (N=1751) had hemoglobin <10 g/dL and had not received an ESA within 8 weeks prior to inclusion in the study. Patients recruited into the ESA-treated NDD-CKD trial (N=1725) had hemoglobin between 8-11 g/dL (US) or 9-12 g/dL (non-US) and were actively treated with an ESA for anemia associated with CKD. Trial periods in both trials include 1) correction/conversion (weeks 0-23); 2) maintenance (weeks 24-52); 3) long-term treatment (week 53 to end of treatment); and 4) safety follow-up (end-of-treatment to 4 weeks later). The primary safety endpoint is time to first adjudicated major adverse cardiovascular event, defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke, pooled across both trials. The primary efficacy endpoint in each trial is change in hemoglobin from baseline to primary evaluation period (weeks 24-36), comparing vadadustat vs darbepoetin alfa treatment groups. Demographics and baseline characteristics were similar among patients in both trials and broadly representative of the NDD-CKD population. These trials will help to evaluate the safety and efficacy of vadadustat for management of anemia associated with NDD-CKD.

View details for DOI 10.1016/j.ahj.2020.10.068

View details for PubMedID 33129989