Clinical trial NCT04117113: Study to Collect Information About Invasive Disease Caused by Extraintestinal Pathogenic Escherichia Coli-2 (EXPECT-2)
Official title: Prospective Epidemiological Study to Estimate the O-serotype Distribution of Extraintestinal Pathogenic Escherichia Coli (ExPEC) Isolated From Hospitalized Patients Aged 60 Years or Older With Invasive ExPEC Disease (IED) and to Evaluate the Clinical Case Definition and Risk Factors.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: E. Coli Infection
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Janssen Research & Development, LLC
name: Innovative Medicines Initiative
First posted: 2019-10-07
Enrollment: 238
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients hospitalized and having culture-confirmed IED.

Brief summary: The purpose of this study is to collect information from study participants who are hospitalized with an invasive disease caused by Extraintestinal pathogenic E. coli (ExPEC). This information will be used to support the development of a new vaccine to prevent Extraintestinal pathogenic Escherichia coli (ExPEC). E. coli bacteria are a leading cause of serious infections. Especially adults older than 60 years have a higher risk of developing such infections. To date, there is no vaccine available to prevent E. coli infections. To support the development of a vaccine, more information about E. coli infections is first needed. This information will be collected in the current study, such as:

* Medical information such as medical history, diagnosis, duration of hospitalization
* Treatment and outcome of the Extraintestinal pathogenic Escherichia coli (ExPEC)
* Laboratory information

Detailed description: Janssen Research \& Development is developing ExPEC10V, a 10-valent conjugate vaccine comprising the 10 most predominant O-polysaccharides of ExPEC.

Invasive ExPEC Disease (IED) is defined as an acute illness consistent with bacterial infection that is microbiologically confirmed either by the isolation and identification of E. coli from blood or other normally sterile body sites, or by the isolation and identification of E. coli from urine in a patient with signs and symptoms of invasive disease (presence of systemic inflammatory response syndrome \[SIRS\], sepsis or septic shock) and no other identifiable source of infection.

ExPEC is the most common cause of infection in humans resulting from gram-negative bacteria. ExPEC comprises a pathogenic group of E. coli strains, possessing the ability to colonize and infect normally sterile body sites and to cause Invasive ExPEC Disease (IED).

ExPEC causes the vast majority of urinary tract infections (UTIs), is the second most frequent cause of neonatal bacteremia and meningitis, and is a leading cause of adult IED, in particular bacteremia and sepsis.

Although IED affects all age categories, adults aged 60 years or older have an increased risk of developing IED, including bacteremia and sepsis. The incidence of community-acquired ExPEC bacteremia increases with age, occurring at a rate of 150/100,000 person-years in the United States (US) adults aged 65 years and older, and 452/100,000 person-years in adults aged 85 years and older. Similar trends have been observed in Europe. In the US, it is estimated that up to 40,000 patients die annually due to IED, in particular from E. coli sepsis. Overall case-fatality rates for ExPEC bacteremia range from 13% to 19% but may be much higher (up to 60%) in the elderly with healthcare-associated infections.

The increase in multidrug resistance (ie, resistance to two or more antibiotic classes) among ExPEC strains, such as E. coli sequence type 131:O25B, represents a major challenge for prevention and management of ExPEC infections. Global morbidity, hospitalization and mortality rates due to ExPEC infections are substantial and increasing due to aging populations and increasing prevalence of antibiotic resistant ExPEC strains, and associated with increasing healthcare costs in both Europe and the US.

This hospital-based prospective epidemiological study will assess the O-serotype and O-genotype distribution in E. coli isolates causing IED overall and by subgroup based on risk factors. Detailed demographic and clinical data, including information on hospital routes, from patients with IED will be collected in this study to further characterize the clinical setting in this patient population. This study will also provide data to compare the clinical criteria of IED used by the study site with the proposed Phase 3 clinical case definition for IED in adults aged 60 years or older for future clinical studies in this patient population. No study drug will be administered in this non interventional study.

Eligibility criteria: Inclusion Criteria:

* Patients aged 60 years or older and hospitalized for IED at the start of the study.
* Culture confirmation of E. coli (1) in normally sterile body sites including blood, and/or (2) in urine in the presence of clinical criteria of an invasive infection (raise in SOFA score \>1, sepsis, or septic shock consequent to the infection).
* For those countries and/or study sites where no waiver for informed consent/assent has been obtained prior to data collection, eligible patients must sign a participation agreement/ICF/IAF allowing data collection and source data verification in accordance with local requirements and/or sponsor policy. For deceased patients, a participation agreement/ICF/IAF must be signed by the patient's next of kin.

Exclusion Criteria:

• There are no exclusion criteria for this study.

Primary outcomes:
measure: Distribution of E. coli O-serotypes causing IED in adults aged 60 years or older, as percentage of the total study population.
timeFrame: 12 months
measure: Distribution of E. coli O-genotypes causing IED in adults aged 60 years or older, as percentage of the total study population.
timeFrame: 12 months
measure: Distribution of IED in adults aged 60 years or older over the following clinical case definitions: "Pyelonephritis", "Urosepsis", "Meningitis", "Arthritis", "Sepsis of unknown origin" and "Others", as a percentage of the total study population.
timeFrame: 12 months
Secondary outcomes:
measure: Proportion of non-bacteremic and bacteremic IED of the total number of IED cases.
timeFrame: 12 months
measure: Listing of IED patients with specific risk factors for IED as a proportion of all IED patients.
timeFrame: 12 months
measure: Type of infection (community acquired, hospital-acquired or healthcare-associated) .
timeFrame: 12 months
measure: Source of infection (presence of an infectious focus within 30 days prior to IED).
timeFrame: 12 months
measure: Susceptibility of the cultured E. coli strains to antibiotics as determined by EUCAST standards (version9.0) to β-lactam antibiotics.
timeFrame: 12 months
measure: O-antigen expression profiles
timeFrame: 12 months
measure: Mortality associated with IED
timeFrame: 12 months
measure: Department where patient is presented/admitted to the hospital (emergency ward, general ward, intensive care unit)
timeFrame: 12 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Clinical Research Institute
state: North Carolina
city: Greater Sudbury
country: Canada
facility: Duke Clinical Research Institute
city: Limoges
country: France
facility: CHU Limoges - CIC
city: Köln
country: Germany
facility: UKK Uniclinic Cologne
city: Verona
country: Italy
facility: University of Verona
city: Tokyo
country: Japan
facility: Janssen Pharmaceutical K.K.
state: Chiyoda-ku
city: Sevilla
country: Spain
facility: Andalusian Public Foundation for Health Research Management in Seville (FISEVI)
city: Oxford
country: United Kingdom
facility: University of Oxford
Study officials:
affiliation: UMC Utrecht
name: Miquel B Ekkelenkamp, MD
role: PRINCIPAL_INVESTIGATOR
References: