Background incidence of serum creatinine threshold rises in a predominantly female clinical trial population without underlying renal disease

Objective: Serum creatinine (Cr) is used to monitor renal function during pre-marketing clinical trials. Standard thresholds for a serum creatinine (Cr) increase predictive of renal injury remain to be established in this setting.

Study design and setting: Aggregated clinical trial data were utilized to evaluate the background frequency of Cr increases of ≥ 0.3 mg/dl and ≥ 0.5 mg/dl from baseline.

Results: Ten thousand and eighteen subjects who participated in 15 clinical trials were included: 311 (4%) male, 7521 (96%) female, mean age of 48.1 years. Mean follow-up time was 6 months. The incidence of Cr increase ≥ 0.3 mg/dl from baseline was 7.5 per 1000 person-months (95%CI 6.81-8.24) and 1.2 per 1000 person-months (95%CI 0.94-1.52) for ≥ 0.5 mg/dl. The Cr increase was sustained at the following visit in 15.9% of subjects with a Cr increase of 0.3 mg/dl, and in 8.9% of those with a 0.5 mg/dl increase from baseline.

Conclusion: A sustained increase in Cr of 0.5 mg/dl from baseline as a stopping criteria for potential nephrotoxicity would have resulted in study drug cessation in approximately 1 in 1000 participants in this selected clinical trial population and would not have caused undue clinical trial attrition.