Clinical trial NCT02573571: Personalized Needs in Clostridium Difficile Infections
Official title: Scoring Personalized Needs in Clostridium Difficile Infections for Fidaxomixin Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Biologic Markers
Clinical Markers
Keywords: single nucleotide polymorphisms
cytokines
microbiome
Lead sponsor: University of Athens
Sponsor class: OTHER
Collaborators: name: Hellenic Sepsis Study Group
First posted: 2015-10-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Clostridium difficile-associated diarrhea

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age equal to or more than 18 years
2. Both genders
3. Diarrhea defined as at least 3 episodes of unformed stools in the last 24 hours according to the Bristol stool chart
4. Presence of C.difficile in stool. This is defined as any stool sample positive for the presence of glutamate dehydrogenase (GDH) and for the presence of toxin A and/or B.

Exclusion Criteria:

1. No exclusion criteria exist

Primary outcomes:
measure: Definition of prognostic biomarker
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Athens
country: Greece
facility: 5th Department of Internal Medicine, Evangelismos Athens General Hospital
city: Athens
country: Greece
facility: 1st Department of Internal Medicine, "G.Gennimatas" General hospital
city: Athens
country: Greece
facility: 1st Department of Internal Medicine, Laikon General Hospital
city: Athens
country: Greece
facility: 3rd Department of Internal Medicine, Sotiria General Hospital
city: Athens
country: Greece
facility: 4th Department of Internal Medicine, ATTIKON University Hospital
city: Athens
country: Greece
facility: 2nd Department of Internal Medicine, Sismanogleion General Hospital
city: Magoula
country: Greece
facility: 1st Department of Internal Medicine, Thriassio General Hospital
city: Magoula
country: Greece
facility: 2nd Department of Internal Medicine, Thriasio General Hospital
city: Maroúsi
country: Greece
facility: 2nd Department of Oncology, Mitera Hospital
city: Piraeus
country: Greece
facility: Infections Unit Tzaneion General Hospital
city: Pátra
country: Greece
facility: Department of Internal Medicine, Patras University Hospital
city: Thessaloniki
country: Greece
facility: 1st Department of Internal Medicine, AHEPA University Hospital
Study officials:
affiliation: Evangelismos Athens General Hospital
name: Athanasios Skoutelis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Attikon Hospital
name: Evangelos J Giamarellos-Bourboulis, MD, PhD
role: STUDY_CHAIR
affiliation: Tzaneion Piraeus General Hospital
name: George Chrysos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Thriassio Elefsis General Hospital
name: Styliani Symbardi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Thriassio Elefsis General Hospital
name: Zoi Alexiou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sotiria General Hospital
name: Kostantinos Syrigos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Laikon Athens General Hospital
name: George Daikos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: G.Gennimatas Athens General Hospital
name: Panagiotis Gargalianos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sismanogleion General Hospital
name: Malvina Lada, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Patras
name: Charalambos Gogos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mitera General Hospital
name: Ilias Athanasiadis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: AHEPA Thessaloniki University Hospital
name: Symeon Metallidis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rao K, Erb-Downward JR, Walk ST, Micic D, Falkowski N, Santhosh K, Mogle JA, Ring C, Young VB, Huffnagle GB, Aronoff DM. The systemic inflammatory response to Clostridium difficile infection. PLoS One. 2014 Mar 18;9(3):e92578. doi: 10.1371/journal.pone.0092578. eCollection 2014.