A subgroup analysis of data from the EXTEND trial (ClinicalTrial.gov identifier: NCT02254967) comparing an extended-pulsed fidaxomicin regimen with a vancomycin regimen for treating Clostridioides difficile (formerly Clostridium difficile) infection (CDI) suggests extended-pulsed fidaxomicin is an efficacious treatment regardless of baseline factors. The results of this analysis were published in the European Journal of Clinical Microbiology & Infectious Diseases.
The effect of the baseline factors advanced age, cancer diagnosis, CDI severity, prior CDI occurrence, and infection with polymerase chain reaction (PCR)-ribotype 027 were assessed using the EXTEND data. In the original trial, patients age ≥ 60 years received extended-pulsed fidaxomicin consisting of fidaxomicin 200 mg twice daily on days 1 to 5 and once daily on alternate days for days 7 to 25, or vancomycin 125 mg 4 times daily on days 1 through 10.
Subgroup analysis found that rates of the primary end point of sustained clinical cure 30 days after the end of treatment did not differ significantly between extended-pulsed fidaxomicin and vancomycin. Sustained clinical cure 30 days after treatment was observed in 70.1% of patients treated with extended-pulsed fidaxomicin and 59.2% of those given vancomycin, regardless of age, cancer diagnosis, CDI severity, and prior CDI. Of note, in patients with PCR-ribotype 027, rates of sustained clinical cure 30 days after treatment were significantly higher in the extended-pulsed fidaxomicin group than in the vancomycin group; 80% vs 40.9%, respectively (treatment difference, 39.1%; 95% CI, 13.2-64.9; P = .006).
The study authors noted several limitations, including the lack of tapered vancomycin or standard 10-day fidaxomicin regimens as comparators because this would have restricted the feasibility of the study. However, researchers noted that this would have broadened the information available. In addition, the post-hoc analyses results in relation to PCR ribotype were not corrected for multiple testing, but the study investigators expect this would not affect the proportions and confidence intervals, only P values.
This study did benefit from the enrollment of elderly patients, a group not typically enrolled in randomized controlled trials. The results also demonstrated positive outcomes for this difficult-to-treat population. Researchers concluded that despite the small size of the subgroups analyzed, “the results suggest greater efficacy with [extended-pulsed fidaxomicin] versus vancomycin in some patient groups.” Further, the results determined that extended-pulsed fidaxomicin is, “efficacious and well tolerated as a potential treatment for CDI regardless of age, presence of cancer, infection with C difficile PCR-ribotype 027, CDI severity, or prior CDI episodes.”
Cornely OA, Vehreschild MJGT, Adomakoh N, et al. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection: EXTEND study subgroup analyses [published online March 25 2019]. Eur J Clin Microbiol Infect Dis. doi:10.1007/s10096-019-03525-y