Validation of the clinical utility of microRNA as noninvasive biomarkers of cardiac allograft rejection: A prospective longitudinal multicenter study

While studies have shown an association between microRNAs and cardiac rejection, the clinical relevance of a pre-identified miRNA signature as a non-invasive biomarker has never been assessed in prospective multicentric unselected cohorts. To address this unmet need, we designed a prospective study (NCT02672683) including recipients from 11 centers between 08/2016 to 03/2018. The objective was to validate the association between three previously identified circulating microRNA (10a, 92a, 155) and the histopathological diagnosis of rejection. Both relative and absolute (sensitivity analysis) quantifications of microRNAs were performed. Overall, 461 patients were included (831 biopsies, 79 rejections). A per-protocol interim analysis (258 biopsies, 49 rejections) did not find any association between microRNA and rejection (microRNA10-a: OR=1.05, 95%CI=0.87-1.27, p=0.61; 92-a: OR=0.98, 95%CI=0.87-1.10, p=0.68; 155: OR=0.91, 95%CI=0.76-1.10, p=0.33). These results were confirmed in the sensitivity analysis. The analysis of the remaining sera was stopped for futility. This study shows no clinical utility of circulating microRNAs 10a, 92a and 155 monitoring in heart allograft recipients.