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.