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

February 5, 2020 updated by: Azucena Rodriguez Guardado, Hospital Universitario de Cabuenes

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Observational

Enrollment (Anticipated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

For the purpose of the study we define case as a patient with C. difficile infection demonstrated in stool samples in presence of compatible gastrointestinal diseases.

We define a positive microbiological result if the patient had a determination of toxin plus GDH positives or there is colonoscopy or histopathological evidence of pseudomembranous colitis. The discordant cases will be confirmed by PCR, and we consider that infection exits if it is positive Recurrence will be considered if the patient presents a new episode of C. difficile infection if he / she presents again compatible clinical and positive microbiological diagnosis in the 60 days following the previous episode.

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Failing to meet the inclusion criteria
  2. If the positive microbiological results were not associated with clinical features of gastrointestinal infection.
  3. Patients with incomplete data.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
No relapses
Patients with clostridium difficile infections without relapses
Diagnostic test: 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.
Relapsing patiens
Patients with clostridium difficile infections with relapses
Diagnostic test: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of risk factors
Time Frame: 12 weeks
identify risk factors linked to the appearance of serious relapses in patients infected with Clostridium difficile, with special emphasis on the relationship between changes in the patient's microbiota and the appearance of these recurrences.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterization of the circulating strain: profile of resistance, ribotype and presence of virulence factors.
Time Frame: 16 weeks
Characterization of the circulating strain: profile of resistance, ribotype and presence of virulence factors.
16 weeks
Study of the alterations in the microbiome of Clostridium difficile-infected patients with relapsing and non-relapsing.
Time Frame: six months
Study of the alterations in the microbiome of Clostridium difficile-infected patients with relapsing and non-relapsing.
six months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitario de Cabuenes

Collaborators

Merck Sharp & Dohme LLC
Hospital Universitario Central de Asturias
Instituto de Productos Lacteos de Asturias

Investigators

  • Principal Investigator: Azucena Rodriguez Guardado, MdPhd, Hospital Universitario de Cabueñes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

March 1, 2020

Primary Completion (ANTICIPATED)

December 1, 2020

Study Completion (ANTICIPATED)

June 1, 2021

Study Registration Dates

First Submitted

February 5, 2020

First Submitted That Met QC Criteria

February 5, 2020

First Posted (ACTUAL)

February 7, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 7, 2020

Last Update Submitted That Met QC Criteria

February 5, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLOSTRI PROJECT

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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