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

NCT04259931 | Unknown

• 1 other identifier: CLOSTRI PROJECT
• Study Type: observational
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Clostridium Difficile Infection

Keywords

Clostridium difficile; relapse; microbiome

Outcome Measures

Primary Outcomes (1)

• Identification of risk factors

  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 Outcomes (2)

• 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.

  six months

Study Arms (2)

No relapses

Patients with clostridium difficile infections without relapses

Diagnostic Test: microbiome analysis

Relapsing patiens

Patients with clostridium difficile infections with relapses

Diagnostic Test: microbiome analysis

Interventions

microbiome analysis 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.

No relapses; Relapsing patiens

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• If the positive microbiological results were not associated with clinical features of gastrointestinal infection.
• Patients with incomplete data.

Sponsors & Collaborators

• Hospital Universitario de Cabuenes: lead
• Merck Sharp & Dohme LLC: collaborator
• Hospital Universitario Central de Asturias: collaborator
• Instituto de Productos Lacteos de Asturias: collaborator

Related Publications (8)

• 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.

  PMID: 30055221 BACKGROUND

• 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.

  PMID: 29132405 BACKGROUND

• 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.

  PMID: 29336928 BACKGROUND

• 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.

  PMID: 29964230 BACKGROUND

• 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.

  PMID: 30400734 BACKGROUND

• 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.

  PMID: 29903711 BACKGROUND

• 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.

  PMID: 30350418 BACKGROUND

• 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.

  PMID: 23748655 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

stools

MeSH Terms

Conditions

Clostridium Infections; Recurrence

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Azucena Rodriguez Guardado, MdPhd

  Hospital Universitario de Cabuenes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Azucena Rodriguez Guardado, Md Phd

CONTACT

+34985185000; azucenarguardado@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Md PhD

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 7, 2020
• Study Start: March 1, 2020
• Primary Completion: December 1, 2020
• Study Completion: June 1, 2021
• Last Updated: February 7, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share