Clinical trial NCT02896244: AssessmeNT of the Incidence of Clostridium Difficile Infections in Hospitalized Patients on Antibiotic TrEatment
Official title: AssessmeNT of the Incidence of Clostridium Difficile Infections in Hospitalized Patients on Antibiotic TrEatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Clostridium Difficile
Keywords: Clostridium difficile
Clostridium difficile infection
antibiotics
antibiotics associated diarrhea
microbiome
microbiota
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Da Volterra
name: Universitätsklinikum Köln
name: Universiteit Antwerpen
First posted: 2016-09-12
Enrollment: 1007
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged 50 or older receiving oral or intervenous antibiotic treatment with Third or fourth generation cephalosporins, Fluoroquinolones, Penicillins +beta-lactamase inhibitors, Clindamycin, or Carbapenems during hospitalization.

Brief summary: During or after antibiotic treatment, antibiotic residues impair the intestinal microbiota (gut flora) and lead to adverse effects such as the emergence of bacterial resistance or the occurrence antibiotic-associated diarrhoea (AAD) including antibiotic-induced C. difficile infection (CDI). The spread of resistant Gram-negative bacteria and the increasing number and severity of CDI are considered as worldwide public health threats.

Da Volterra is a biotechnology company developing a novel product, DAV132 (a medical device in Europe), intended to prevent these antibiotic adverse effects. Da Volterra is planning to carry out a phase 2-3 randomized controlled trial (RCT) of DAV132 in the prevention of antibiotic-induced CDI. The RCT will involve hospitalized patients aged ≥50 years old and treated with predefined antibiotic classes known to increase the risk of CDI. The incidence of CDI in this population is unknown, yet, incidence is an important determinant for the required sample size.

Therefore, the main objective of the current study is to assess CDI incidence in patients ≥50 years of age treated with predefined antibiotic classes.

In addition, to optimise the target population of the DAV132 RCT, the effect of the predefined antibiotic agents on the intestinal microbiota will be assessed. Furthermore, biomarkers predictive of CDI occurrence might help identify patients at high risk for the disease, which could further optimise the RCT. No validated biomarkers have been described in the literature yet. Assessment of potential biomarkers is another aim of the present study.


Eligibility criteria: Inclusion Criteria:

1. Male or female hospitalized patient.
2. Aged ≥ 50 years old.
3. Initiation of intravenous or oral treatment with intended duration ≥5 days (≥1 day for clindamycin) with at least one of the following antibiotic classes, or treatment scheduled within the next 72 hours:

   * Third or fourth generation cephalosporins
   * Fluoroquinolones
   * Penicillins +beta-lactamase inhibitors
   * Clindamycin
   * Carbapenems
4. Written informed consent provided prior to inclusion.

Exclusion Criteria:

1. Ongoing antibiotic treatment with one of the above classes initiated \>6 hours before inclusion into the study.
2. ICU admission at the time of inclusion or anticipated admission within 48h.
3. Suspected or diagnosed CDI, ongoing treatment for CDI, or diarrhoea at the time of inclusion.
4. Patient with stoma.
5. Subject has been included into this study previously.
6. Patient treated with probiotics to prevent CDI.
7. Patient with any social or logistical condition which in the opinion of the investigator may interfere with the conduct of the study, such as incapacity to well understand, not willing to collaborate, or cannot easily be contacted after discharge.
8. Subject is subject to legal protection.
9. Subject deprived of liberty by judicial or administrative decision.

Primary outcomes:
measure: Clostridium difficile infection
timeFrame: 28 days
Secondary outcomes:
measure: Clostridium difficile infection
timeFrame: 90 days
measure: Antibiotics associated diarrhea
timeFrame: 90 days
measure: Bacterial diversity
timeFrame: 6 days
measure: Urine sulfate levels
timeFrame: 6 days
Other outcomes:
Locations:
city: La Roche-sur-Yon
country: France
facility: CHD Vendee
city: Limoges
country: France
facility: CHU Dupuytren
city: Paris
country: France
facility: APHP Beaujon
city: Paris
country: France
facility: APHP Bichat
city: Paris
country: France
facility: APHP Hôpital Cochin
city: Paris
country: France
facility: Hôpital St Louis
city: Quimper
country: France
facility: CH de Cornouaille
city: Tours
country: France
facility: Centre Hospitalier Universitaire de Tours
city: Aachen
country: Germany
facility: Uniklinik der RWTH
city: Cologne
country: Germany
facility: Uniklinik Köln
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Leipzig
country: Germany
facility: UK Leipzig
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Lübeck
city: Munchen
country: Germany
facility: Klinikum der Universität München
city: Athens
country: Greece
facility: Evangelismos General Hospital of Athens
city: Athens
country: Greece
facility: Ippokratio Hospital of Athens
city: Athens
country: Greece
facility: Laiko General Hospital
city: Athens
country: Greece
facility: University General Hospital ATTIKON
city: Iráklion
country: Greece
facility: University Hospital of Heraklion
city: Utrecht
country: Netherlands
facility: University Medical Center
city: Bucharest
country: Romania
facility: Infectious and Tropical Diseases Hospital "Dr. Victor Babes"
city: Bucharest
country: Romania
facility: The National Institute of Infectious Diseases Matei Bals
city: Cluj Napoca
country: Romania
facility: Cluj Napoca Infectious disease Clinical Hospital
city: Cluj Napoca
country: Romania
facility: Oncology Institute Ion Chiricuta Cluj Napoca
city: Iasi
country: Romania
facility: Clinical Hospital Of Infectious Diseases Of Iasi
city: Barcelona
country: Spain
facility: Bellvitge Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebrón
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
Study officials:
affiliation: UMC Utrecht
name: Marc Bonten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Werkhoven CH, Ducher A, Berkell M, Mysara M, Lammens C, Torre-Cisneros J, Rodriguez-Bano J, Herghea D, Cornely OA, Biehl LM, Bernard L, Dominguez-Luzon MA, Maraki S, Barraud O, Nica M, Jazmati N, Sablier-Gallis F, de Gunzburg J, Mentre F, Malhotra-Kumar S, Bonten MJM, Vehreschild MJGT; ANTICIPATE Study Group. Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics. Nat Commun. 2021 Apr 14;12(1):2240. doi: 10.1038/s41467-021-22269-y.
citation: Berkell M, Mysara M, Xavier BB, van Werkhoven CH, Monsieurs P, Lammens C, Ducher A, Vehreschild MJGT, Goossens H, de Gunzburg J, Bonten MJM, Malhotra-Kumar S; ANTICIPATE study group. Microbiota-based markers predictive of development of Clostridioides difficile infection. Nat Commun. 2021 Apr 14;12(1):2241. doi: 10.1038/s41467-021-22302-0.