Analytical validation of GMEX rapid point-of-care CYP2C19 genotyping system for the CHANCE-2 trial

Background and purpose Rapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events (HR-NICE). Conventional genetic testing methods used in CYP2C19 genotype-guided antiplatelet therapy for patients with HR-NICE did not satisfy the needs of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE)-2 trial. Therefore, we developed the rapid-genotyping GMEX (point-of-care) system to meet the needs of the CHANCE-2 trial. Methods Healthy individuals and patients with history of cardiovascular diseases (n=408) were enrolled from six centres of the CHANCE-2 trial. We compared the laboratory-based genomic test results with Sanger sequencing test results for accuracy verification. Next, we demonstrated the accuracy, timeliness and clinical operability of the GMEX system compared with laboratory-based technology (YZY Kit) to verify whether the GMEX system satisfies the needs of the CHANCE-2 trial. Results Genotypes reported by the GMEX system showed 100% agreement with those determined by using the YZY Kit and Sanger sequencing for all three CYP2C19 alleles (*2, *3 and *17) tested. The average result's turnaround times for the GMEX and YZY Kit methods were 85.0 (IQR: 85.0-86.0) and 1630.0 (IQR: 354.0-7594.0) min (p<0.001), respectively. Conclusions Our data suggest that the GMEX system is a reliable and feasible point-of-care system for rapid CYP2C19 genotyping for the CHANCE-2 trial or related clinical and research applications.

Automated summary

A rapid-genotyping system named GMEX was developed for CYP2C19 genotyping, which showed 100% agreement with traditional laboratory methods in terms of accuracy. The GMEX system demonstrated faster turnaround times compared to the YZY Kit, making it a reliable and feasible point-of-care system for the CHANCE-2 trial and related clinical applications.