Biologic Markers Clinical Trial
Official title:
Scoring Personalized Needs in Clostridium Difficile Infections for Fidaxomixin Therapy
To develop a score that can predict early from diagnosis of Clostridium difficile infection (CDI) the risk for relapse and of unfavorable outcome. This score can be used in the future to identify patients will benefit from fidaxomicin treatment.
Medical world is nowadays witnessing a sudden increase of the incidence of infections by
Clostridium difficile (DCI). This is due in part to the prolongation of survival of patients
with major comorbidities like solid tumor malignancies and lymphomas but also to the
widespread intake of proton pump inhibitors and of wide-spectrum antimicrobials. It is highly
probable that isolates of C.define causing this pandemic are genetically different than
isolates of the same species predominating 20 years ago. This hypothesis is developed based
on data of the epidemiology of CDI: in old times administration of clindamycin and ampicillin
were the main drivers of CDI; recent studies report fluoroquinolones, 2nd and 3rd generation
cephalosporins and even vancomycin (i.e. a drug of choice for CDI) to be linked with the
development of CDI.
One major hurdle in management of CDI is relapse; the risk of relapse is reported as 15-20%
after the first episode; however it is geometrically increased to even 60-80% after the
second episode. As a consequence, management of CDI becomes a major health problem.
Fidaxomicin is a novel compound active against species of C.dificille. Results of two recent
double-blind, randomized, large scale clinical studies have shown that oral treatment for 10
days with fidaxomicin 200mg bid was non-inferior to oral treatment with vancomycin 125mg q6h.
However, the risk of relapse after treatment with vancomycin was close to 25% and with
fidaxomicin close to 15%. This difference was statistically significant in both trials
outscoring the superiority of fidaxomicin over vancomycin for the management of CDI.
Moreover, meta-analysis has shown a significant reduction in mortality by fidaxomicin.
Despite proven superiority, prescription of fidaxomicin is limited to few cases mostly due to
high cost. In many countries prescription is restricted to cases of relapsing CDI. Clinical
feeling coming both from post-marketing experience as well as from published evidence
supports the use of fidaxomicin for cases with risk of death and overt risk of relapse.
However, molecular analysis of the C.difficile pathogen cannot be used as a tool for the
prediction of relapse since in relapse cases pathogens carry less than 2 single nucleotide
variants of the initial isolate. SPECIFY is aiming to develop a score using both clinical and
genetic and biomarker data that can efficiently discriminate patients at risk of severe CDI
and at risk of relapse of CDI. This score can become in future a tool to discriminate
patients at need for treatment with fidaxomicin instead of traditional treatment with
metronidazole/vancomycin.
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