Personalized Needs in Clostridium Difficile Infections (SPECIFY)

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ClinicalTrials.gov Identifier: NCT02573571

Recruitment Status : Completed

First Posted : October 12, 2015

Last Update Posted : October 5, 2017

Sponsor:

Collaborator:

Hellenic Sepsis Study Group

Information provided by (Responsible Party):

Evangelos J. Giamarellos-Bourboulis, M.D., University of Athens

Study Description

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.

Condition or disease	Intervention/treatment
Biologic Markers Clinical Markers	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 Design

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Study Type :	Observational
Actual Enrollment :	150 participants
Observational Model:	Case-Only
Time Perspective:	Prospective
Official Title:	Scoring Personalized Needs in Clostridium Difficile Infections for Fidaxomixin Therapy
Actual Study Start Date :	October 2015
Actual Primary Completion Date :	December 2016
Actual Study Completion Date :	October 2017

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

Definition of prognostic biomarker [ Time Frame: 12 months ]
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

Biospecimen Retention: Samples With DNA

Whole blood for human DNA extraction and human stool for whole bacterial DNA extraction. Sampling is done on the first day and on disease recurrence

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Patients with Clostridium difficile-associated diarrhea

Criteria

Inclusion Criteria:

Age equal to or more than 18 years
Both genders
Diarrhea defined as at least 3 episodes of unformed stools in the last 24 hours according to the Bristol stool chart
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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02573571

Locations

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Greece
5th Department of Internal Medicine, Evangelismos Athens General Hospital
Athens, Greece, 10676
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, 11527
4th Department of Internal Medicine, ATTIKON University Hospital
Athens, Greece, 12462
2nd Department of Internal Medicine, Sismanogleion General Hospital
Athens, Greece, 15126
1st Department of Internal Medicine, Thriassio General Hospital
Magoula, Greece, 10918
2nd Department of Internal Medicine, Thriasio General Hospital
Magoula, Greece, 10918
2nd Department of Oncology, Mitera Hospital
Maroúsi, Greece, 15123
Infections Unit Tzaneion General Hospital
Piraeus, Greece
Department of Internal Medicine, Patras University Hospital
Pátra, Greece, 36504
1st Department of Internal Medicine, AHEPA University Hospital
Thessaloniki, Greece, 54248

Sponsors and Collaborators

University of Athens

Hellenic Sepsis Study Group

Investigators

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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

More Information

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.

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Responsible Party:	Evangelos J. Giamarellos-Bourboulis, M.D., Associate Professor of Internal Medicine, University of Athens
ClinicalTrials.gov Identifier:	NCT02573571
Other Study ID Numbers:	CL01
First Posted:	October 12, 2015 Key Record Dates
Last Update Posted:	October 5, 2017
Last Verified:	October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Evangelos J. Giamarellos-Bourboulis, M.D., University of Athens:


single nucleotide polymorphisms cytokines microbiome

Additional relevant MeSH terms:

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Clostridium Infections Infections Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses

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