Personalized Needs in Clostridium Difficile Infections

Biologic Markers Clinical Trial

— SPECIFY  

Official title:

Scoring Personalized Needs in Clostridium Difficile Infections for Fidaxomixin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02573571
• Other study ID #: CL01
• Status: Completed
• Phase: N/A
• First received: October 8, 2015
• Last updated: October 3, 2017
• Start date: October 2015
• Est. completion date: October 2017

Study information

• Verified date: October 2017
• Source: University of Athens
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: October 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Biologic Markers
• Clinical Markers

Intervention

Other:
• Development of biomarkers
Blood sampling

Locations

Country	Name	City	State
Greece	1st Department of Internal Medicine, "G.Gennimatas" General hospital	Athens
Greece	1st Department of Internal Medicine, Laikon General Hospital	Athens
Greece	2nd Department of Internal Medicine, Sismanogleion General Hospital	Athens
Greece	3rd Department of Internal Medicine, Sotiria General Hospital	Athens
Greece	4th Department of Internal Medicine, ATTIKON University Hospital	Athens
Greece	5th Department of Internal Medicine, Evangelismos Athens General Hospital	Athens
Greece	1st Department of Internal Medicine, Thriassio General Hospital	Magoula
Greece	2nd Department of Internal Medicine, Thriasio General Hospital	Magoula
Greece	2nd Department of Oncology, Mitera Hospital	Maroúsi
Greece	Department of Internal Medicine, Patras University Hospital	Pátra
Greece	Infections Unit Tzaneion General Hospital	Piraeus
Greece	1st Department of Internal Medicine, AHEPA University Hospital	Thessaloniki

Sponsors (2)

Lead Sponsor	Collaborator
University of Athens	Hellenic Sepsis Study Group

Country where clinical trial is conducted

Greece, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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