Personalized Needs in Clostridium Difficile Infections (SPECIFY)

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.

Study Overview

• Status: Completed
• Conditions: Biologic Markers; Clinical Markers
• Intervention / Treatment: Other: Development of biomarkers

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.

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 10676
    • 5th Department of Internal Medicine, Evangelismos Athens General Hospital
  • Athens, Greece, 11527
    • 1st Department of Internal Medicine, "G.Gennimatas" General hospital
  • Athens, Greece, 11527
    • 1st Department of Internal Medicine, Laikon General Hospital
  • Athens, Greece, 11527
    • 3rd Department of Internal Medicine, Sotiria General Hospital
  • Athens, Greece, 12462
    • 4th Department of Internal Medicine, Attikon University Hospital
  • Athens, Greece, 15126
    • 2nd Department of Internal Medicine, Sismanogleion General Hospital
  • Magoula, Greece, 10918
    • 1st Department of Internal Medicine, Thriassio General Hospital
  • Magoula, Greece, 10918
    • 2nd Department of Internal Medicine, Thriasio General Hospital
  • Maroúsi, Greece, 15123
    • 2nd Department of Oncology, Mitera Hospital
  • Piraeus, Greece
    • Infections Unit Tzaneion General Hospital
  • Pátra, Greece, 36504
    • Department of Internal Medicine, Patras University Hospital
  • Thessaloniki, Greece, 54248
    • 1st Department of Internal Medicine, AHEPA University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Clostridium difficile-associated diarrhea

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Clostridium difficile infection; Patients with Clostridium difficile-associated diarrhea for development of biomarkers	Other: Development of biomarkers; Blood sampling; Other Names: Single nucleotide polymorphisms; Serum cytokines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Definition of prognostic biomarker	Patients with positive score and unfavorable outcome. Unfavorable outcome is defined as at least one of the following: a) number of patients with severe infection at disease onset; b) number of patients who progress into severe infection; c) number of patients with disease recurrence; and d) number of patients who die	12 months

Collaborators and Investigators

• Sponsor: University of Athens
• Collaborators: Hellenic Sepsis Study Group
• Investigators: Principal Investigator: Athanasios Skoutelis, MD, Evangelismos Athens General Hospital; Study Chair: Evangelos J Giamarellos-Bourboulis, MD, PhD, Attikon Hospital; Principal Investigator: George Chrysos, MD, PhD, Tzaneion Piraeus General Hospital; Principal Investigator: Styliani Symbardi, MD, PhD, Thriassio Elefsis General Hospital; Principal Investigator: Zoi Alexiou, MD, PhD, Thriassio Elefsis General Hospital; Principal Investigator: Kostantinos Syrigos, MD, PhD, Sotiria General Hospital; Principal Investigator: George Daikos, MD, PhD, Laikon Athens General Hospital; Principal Investigator: Panagiotis Gargalianos, MD, PhD, G.Gennimatas Athens General Hospital; Principal Investigator: Malvina Lada, MD, PhD, Sismanogleion General Hospital; Principal Investigator: Charalambos Gogos, MD, PhD, University Hospital of Patras; Principal Investigator: Ilias Athanasiadis, MD, PhD, Mitera General Hospital; Principal Investigator: Symeon Metallidis, MD, PhD, AHEPA Thessaloniki University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: October 8, 2015
• First Submitted That Met QC Criteria: October 9, 2015
• First Posted (Estimate): October 12, 2015

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: October 3, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: single nucleotide polymorphisms; cytokines; microbiome
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections
• Other Study ID Numbers: CL01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No