Background The serum calcification propensity test (or T50 test) might become a standard tool for the assessment of vascular calcification risk, and T50 might be a valuable biomarker in clinical trials of treatments intended to slow the progression of vascular calcification. Literature data suggest that non-calcium-containing phosphate binders can influence T50 in chronic dialyzed patients. However, it is not clear whether similar interventions are effective in patients at earlier stages of chronic kidney disease (CKD). Methods The “FGF23 Reduction efficacy of a new Phosphate Binder in CKD” (FRENCH) trial was a multi-centre, double-blind, placebo-controlled, randomized trial of sevelamer carbonate in participants with stage 3b/4 CKD. In this subanalysis of the FRENCH data, T50 and other laboratory variables (including fetuin A, and ionized and total magnesium) were measured centrally at baseline and after 12 weeks of treatment. Results A total of 96 patients were screened; 78 (55 men and 23 women) met the inclusion criteria and were randomized to receive placebo (n=39) or sevelamer carbonate (n=39). The median [interquartile range] patient age was 66 [56-72], the median eGFR was 25 [21-30] mL/min/1.73m², and the mean T50 was 335 (82) minutes. In a linear regression model, T50 was independently associated with serum ionized magnesium, fetuin-A and bicarbonate levels; and inversely associated with phosphate concentration. The within-group changes in the mean [95% confidence interval] T50 between week 0 and week 12 were not significant in the sevelamer group or the placebo group (4.6 [-13.6; 22.8] minutes (p=0.61) and 7.8 [-16.4; 32.1] minutes (p=0.51), respectively). Furthermore, we did not observe significant changes in fetuin-A and magnesium levels. Conclusion A 12-week course of the non-calcium-containing phosphate binder sevelamer carbonate was not associated with a significant change in T50 in patients with stage 3b/4 CKD. Phosphate binders might not be an effective strategy for modifying serum calcification propensity in non-dialysis-dependent patients with CKD.