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T 09: Albuminuria in Cardiovascular Outcome Trials: Balancing Event and Recruitment Rates
Quintiles United Kingdom
Describe the rationale for use albuminuria (UACr) as a biomarker in cardiovascular outcome trials (CVOT)
• Identify challenges to recruitment that albuminuria and UACr cause when required in protocol inclusion criteria
ORAL PRESENTATION SCHEDULED: Session 1A at 10:00 - 10:10 AM
We reviewed data from several completed and ongoing cardiovascular outcome studies. Screening and Baseline UACR values were analysed and correlated with cardiovascular event rates. We also reviewed international and local guidelines for albuminuria testing checking recommended frequency and method.
The preliminary results of performed analyses suggest that addition of microalbuminuria to the inclusion criteria list in CVOTs significantly increases screen failure rate, even in subjects with diabetes or hypertension. In subjects with albuminuria, major adverse cardiovascular event rate (MACE primary study endpoints in CVOT) is higher as compared to subjects without micro- or macro-albuminuria. However, the enrichment of MACE events offered by micro- and macro-albuminuria does not appear to outweigh the negative impact on overall study duration caused by high screen failure rate related to the requirement of pre-existing microalbuminuria. Available guidelines for albuminuria testing are general and focused primarily on subjects with diabetes and hypertension, making addition of documented history of albuminuria to the eligibility criteria unnecessary and impractical.
With well-established predictive value of albuminuria, addition of UACR into the list of risk factors used in numerous CVOT protocols seems to be logical. However, there are several limitations of this approach. First, UACR is not routinely measured in many countries, even in diabetic subjects, so requirement of UACR testing in global trials can introduce regional challenges to patient enrolment. Additionally, there is a poor correlation between results of commonly used dipstick tests or local results obtained from the random urine samples and UACR values obtained from the central laboratories, making pre-screening of subjects very challenging. Unfortunately, attempts to mitigate this challenge by requiring standardization of urine sample collection leads to other operational challenges, which overall contributes to the high variability of screening and randomisation UACR results and higher screen failure rates.