PROSPECTIVE STUDY OF PREDISPOSING FACTORS OF REFRACTARY Clostridium Difficile INFECTION. INFLUENCE OF THE GUT MICROBIOMA

NCT ID: NCT04259931

Last Updated: 2020-02-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-03-01

Study Completion Date

2021-06-01

Brief Summary

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A higher frequency of recurrences in the University Hospital of Cabueñes (HUCAB) than in other hospitals in our area, including Central University Hospital of Asturias (HUCA) has been found. This increase does not seem to be related to underlying diseases, age, sex or predisposing factors classically described in this type of infection. This high rate of recurrence, together with the absence of response to all conventionally used antibiotic treatments, has important repercussions in the morbidity and mortality of patients, in the ecology of the hospital due to the risk of transmission of a strain of major severity and in the high costs associated with an increase in the hospitalization days of these patients, as well as in an eventual transfer of these to other structures specialized in fecal transplantation.

Two hypotheses are proposed to explain the higher frequency reported:

Hypothesis 1. There are alterations of the microbiome in patients with severe recurrences that favor the appearance of these.

Hypothesis 2. The circulating strain in the hospital has intrinsic characteristics that make it more virulent, such as the presence of virulence or multiresistance factors.

For this reason we design a descriptive, prospective multicentric study that will include all patients older than 18 years diagnosed with C difficile infection at the Central University Hospital of Asturias and the University Hospital of Cabueñes during the year 2020-2021

Detailed Description

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Clostridium difficile infection (CDI) is currently a priority public health problem. In recent decades, the exponential increase in the incidence and severity of CDI has forced to develop new and better methods of treatment and control of the infection. Currently, it is the most common cause of nosocomial infectious diarrhea, with 20 cases per 100,000 people / year or 15 cases per 1000 hospital discharges.

The identification of risk factors for the CDI has become one of the basic pillars to study in order to improve epidemiological control. Classically known risk factors associated with CDI (hospitalization, advanced age, antibiotic prescription, gastrointestinal surgery) have joined in recent years as a result of recent research (for example, the use of proton pump inhibitors).

One of the main problems offered by the management of the CDI is the role of recurrences. There is no consensus about the definition of recurrence in the international CDI management guidelines, however, it is usually established as the presence of diarrhea in the 30 days after an CDI that had presented positive toxin.

The recurrence of the CDI implies a new level of complexity when dealing with the management of this infection: the recurrence percentages range between 15-50% after an initial episode, establishing in recent studies that it could be reasonable to estimate that 20-25% of the patients will present a recurrence in the first 30 days after finishing the antibiotic treatment for the CDI. In addition, after the first recurrence the risk of presenting a new one increases up to 45%, and the risk of subsequent recurrences doubles after 2 or more recurrences.

The study of recurrence in the CDI is the objective of multiple studies. Its importance is based on both epidemiological and economic reasons, since each episode of recurrence increases hospital costs (in a study carried out by the Spanish Ministry of Health in 2013, it was estimated that each new episode of recurrence entailed an increase in the cost of 1000 euros)

The new lines of recurrence research in CDI try to find associations between severity, microbiome, demographic findings and new risk factors and the possibility of recurrence, in order to try to predict it by developing clinical models predictive of recurrence, which, until now, they only have a very limited role.

Previous data collected by our working group show important differences in the behavior of Clostridium difficile infection between the Central University Hospital of Asturias (HUCA) and the University Hospital of Cabueñes (HUCAB), among which the high number of recurrences and failures to conventional treatments in the latter, being necessary even fecal transplantation as a last therapeutic resource.

In 2017, there were 27 patients with Clostridium difficile infection in the HUCAB, of whom 8 (33.3%) relapsed. In 2018, 4 (22.2%) of 18 patients relapsed, three of them more than three times. Analyzing the characteristics of patients with recurrence within the HUCAB during the years 2017-2018, we found that recurrences are significantly more frequent in patients treated with metronidazole, although this is possibly due to the fact that it is the drug used systematically as the first choice, and diagnosed with hepatopathy without differences between the other treatments, which supports the hypothesis that the differences are due more to the behavior of the strain than to the clinical characteristics of the patients.

A higher frequency of recurrences in the University Hospital of Cabueñes (HUCAB) than in other hospitals in our area, including Central University Hospital of Asturias (HUCA) has been found. This increase does not seem to be related to underlying diseases, age, sex or predisposing factors classically described in this type of infection. This high rate of recurrence, together with the absence of response to all conventionally used antibiotic treatments, has important repercussions in the morbidity and mortality of patients, in the ecology of the hospital due to the risk of transmission of a strain of major severity and in the high costs associated with an increase in the hospitalization days of these patients, as well as in an eventual transfer of these to other structures specialized in fecal transplantation.

Two hypotheses are proposed to explain the higher frequency reported:

Hypothesis 1. There are alterations of the microbiome in patients with severe recurrences that favor the appearance of these.

Hypothesis 2. The circulating strain in the hospital has intrinsic characteristics that make it more virulent, such as the presence of virulence or multiresistance factors We design a descriptive, prospective multicentric study that will include all patients older than 18 years diagnosed with C difficile infection at the Central University Hospital of Asturias and the University Hospital of Cabueñes during the year 2020-2021

Conditions

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Clostridium Difficile Infection

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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No relapses

Patients with clostridium difficile infections without relapses

microbiome analysis

Intervention Type DIAGNOSTIC_TEST

gut microbiome composition of C. difficile infected patients with relapsing (basal, at the end of first treatment, at the begin of the relapses and at four and twelve weeks after definitive treatment) and non-relapsing ( basal and four and twelve week after treatment) , will be analyzed.

Relapsing patiens

Patients with clostridium difficile infections with relapses

microbiome analysis

Intervention Type DIAGNOSTIC_TEST

gut microbiome composition of C. difficile infected patients with relapsing (basal, at the end of first treatment, at the begin of the relapses and at four and twelve weeks after definitive treatment) and non-relapsing ( basal and four and twelve week after treatment) , will be analyzed.

Interventions

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microbiome analysis

gut microbiome composition of C. difficile infected patients with relapsing (basal, at the end of first treatment, at the begin of the relapses and at four and twelve weeks after definitive treatment) and non-relapsing ( basal and four and twelve week after treatment) , will be analyzed.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

1. Diagnosed of C. difficile infection
2. Age older than 18 years old.

2. If the positive microbiological results were not associated with clinical features of gastrointestinal infection.
3. Patients with incomplete data.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Hospital Universitario Central de Asturias

OTHER

Sponsor Role collaborator

Instituto de Productos Lacteos de Asturias

UNKNOWN

Sponsor Role collaborator

Hospital Universitario de Cabuenes

OTHER

Sponsor Role lead

Responsible Party

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Azucena Rodriguez Guardado

Md PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Azucena Rodriguez Guardado, MdPhd

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario de Cabuenes

Central Contacts

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Azucena Rodriguez Guardado, Md Phd

Role: CONTACT

+34985185000 ext. 72442

References

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Bradley CW, Burdett H, Holden KL, Holden E, Garvey MI. How do we define recurrence in Clostridium difficile infection? J Hosp Infect. 2019 Jun;102(2):171-173. doi: 10.1016/j.jhin.2018.07.026. Epub 2018 Jul 26. No abstract available.

Reference Type BACKGROUND
PMID: 30055221 (View on PubMed)

Pakpour S, Bhanvadia A, Zhu R, Amarnani A, Gibbons SM, Gurry T, Alm EJ, Martello LA. Identifying predictive features of Clostridium difficile infection recurrence before, during, and after primary antibiotic treatment. Microbiome. 2017 Nov 13;5(1):148. doi: 10.1186/s40168-017-0368-1.

Reference Type BACKGROUND
PMID: 29132405 (View on PubMed)

Petrosillo N. Tackling the recurrence of Clostridium difficile infection. Med Mal Infect. 2018 Feb;48(1):18-22. doi: 10.1016/j.medmal.2017.10.007. Epub 2018 Jan 12.

Reference Type BACKGROUND
PMID: 29336928 (View on PubMed)

Falcone M, Tiseo G, Iraci F, Raponi G, Goldoni P, Delle Rose D, Santino I, Carfagna P, Murri R, Fantoni M, Fontana C, Sanguinetti M, Farcomeni A, Antonelli G, Aceti A, Mastroianni C, Andreoni M, Cauda R, Petrosillo N, Venditti M. Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes. Clin Microbiol Infect. 2019 Apr;25(4):474-480. doi: 10.1016/j.cmi.2018.06.020. Epub 2018 Jun 28.

Reference Type BACKGROUND
PMID: 29964230 (View on PubMed)

Song JH, Kim YS. Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention. Gut Liver. 2019 Jan 15;13(1):16-24. doi: 10.5009/gnl18071.

Reference Type BACKGROUND
PMID: 30400734 (View on PubMed)

Ford DC, Schroeder MC, Ince D, Ernst EJ. Cost-effectiveness analysis of initial treatment strategies for mild-to-moderate Clostridium difficile infection in hospitalized patients. Am J Health Syst Pharm. 2018 Aug 1;75(15):1110-1121. doi: 10.2146/ajhp170554. Epub 2018 Jun 14.

Reference Type BACKGROUND
PMID: 29903711 (View on PubMed)

Tieu JD, Williams RJ 2nd, Skrepnek GH, Gentry CA. Clinical outcomes of fidaxomicin vs oral vancomycin in recurrent Clostridium difficile infection. J Clin Pharm Ther. 2019 Apr;44(2):220-228. doi: 10.1111/jcpt.12771. Epub 2018 Oct 22.

Reference Type BACKGROUND
PMID: 30350418 (View on PubMed)

Asensio A, Bouza E, Grau S, Rubio-Rodriguez D, Rubio-Terres C. [Cost of Clostridium difficile associated diarrhea in Spain]. Rev Esp Salud Publica. 2013 Jan-Feb;87(1):25-33. doi: 10.4321/S1135-57272013000100004. Spanish.

Reference Type BACKGROUND
PMID: 23748655 (View on PubMed)

Other Identifiers

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CLOSTRI PROJECT

Identifier Type: -

Identifier Source: org_study_id

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