Primary objective:To determine the incidence of Clostridium difficile infection (CDI) in hospitalized patients aged * 50 years old and receiving oral or intravenous fluoroquinolones, cephalosporins, penicillins + beta-lactamase inhibitors,…
ID
Source
Brief title
Condition
- Gastrointestinal infections
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Incidence of CDI within 28 days of initiation of antibiotic treatment.
Secondary outcome
Secondary endpoints:
1. Incidence of CDI within 90 days of antibiotic treatment initiation.
2. Incidence of AAD within 28 days of antibiotic treatment initiation.
3. Incidence of AAD within 90 days of antibiotic treatment initiation.
4. Incidence of CDI and AAD 28 and 90 days after antibiotic treatment
initiation by class of antibiotics.
5. Incidence of CDI and AAD 28 and 90 days after antibiotic treatment
initiation by C. difficile colonization status at the start of antibiotic
treatment.
6. Time from the start of antibiotic treatment to occurrence of CDI.
7. Incidence of CDI in patients with previous CDI.
8. Bacterial diversity of the intestinal microbiome, as assessed by the Shannon
diversity index using 16S rRNA gene profiling, at the start of antibiotic
treatment in patients developing CDI, patients developing AAD (including CDI),
patients developing non-CDI AAD, and non-diarrheic patients.
9. Change from baseline to day 6 of bacterial diversity and composition of the
intestinal microbiome as assessed respectively by the Shannon diversity index
and the Spearman rank correlation coefficient of the relative abundance of OTUs
between the start of the antibiotic treatment and day 6 measured by 16S rRNA
gene sequencing, by antibiotic class.
10. 3-3-indoxyl sulfate levels in urine at the start of antibiotic treatment in
patients developing CDI, patients developing AAD (including CDI), patients
developing non-CDI AAD, and non-diarrheic patients.
11. Relationship between 3-3-indoxyl sulfate levels in urine and bacterial
diversity and composition of the intestinal microbiome, both at the start of
antibiotic treatment and at day 6.
Exploratory endpoints:
1. Number and proportion of study sites/hospitals which included patients in
the present study within the desired time window, overall and by country.
2. Number and proportion of study sites/hospitals able to collect the required
information on study outcomes (occurrence of AAD/CDI) during hospitalisation
and after discharge from hospital, overall and by country.
3. Description of the identified potential bottlenecks for successful execution
of the DAV132 RCT, overall and by country.
4. Antibiotic consumption, length of stay in hospital, length of stay in ICU,
and mortality in patients with CDI compared to patients not developing CDI,
overall and by country.
5. Estimated costs of CDI management, overall and by country.
Background 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.
Study objective
Primary objective:
To determine the incidence of Clostridium difficile infection (CDI) in
hospitalized patients aged * 50 years old and receiving oral or intravenous
fluoroquinolones, cephalosporins, penicillins + beta-lactamase inhibitors,
carbapenems, and/or clindamycin.
Secondary objectives
1. To determine the incidence of antibiotic-associated diarrhoea (AAD,
including CDI).
2. To quantify the predictive value of asymptomatic carriage of toxin-producing
C. difficile at the start of antibiotic treatment for the occurrence of CDI/AAD.
3. To determine the incidence of CDI in patients with previous CDI.
4. To assess if bacterial diversity of the intestinal microbiome at the start
of antibiotic treatment predicts the occurrence of CDI/AAD.
5. To determine the changes of intestinal microbiome bacterial diversity and
composition induced, by antibiotic class.
6. To assess if 3-indoxyl sulfate levels in urine at the start of antibiotic
treatment predict the occurrence of CDI/AAD.
7. To quantify the correlation between 3-indoxyl sulfate levels in urine and
the disruption of the intestinal microbiome at the start of and during
antibiotic treatment.
Exploratory objectives
In preparation of a phase II/III RCT of DAV132 the following exploratory
objectives are specified:
1. To determine the capability of study sites/hospitals to include patients in
the present study within the desired time window.
2. To determine the ability of study sites/hospitals to collect the required
information on study outcomes (occurrence of AAD/CDI) during hospitalisation
and after discharge from hospital.
3. To identify and describe potential bottlenecks (and solutions) for
successful execution of the RCT.
4. To characterize the outcome of CDI.
5. To evaluate the cost of CDI management.
Study design
European multicenter, hospital-based, prospective, observational cohort study.
Study burden and risks
Burden: collection of three rectal swabs at two time points. Collection of two
urine samples at two time points. Collection of stool sample in case of
diarrhea. Completion of the patient diary containing three yes/no questions
daily for 90 days.
Risk: temporary uncomfortable feeling from the rectal swabs.
Benefit: there is no direct benefit for patients to participate in the study.
Group relatedness: the subject of investigation is related to the study
population in that all patients treated with antibiotics are at risk of
developing Clostridium difficile infections.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
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. Subject has been included into this study previously.
5. Patient treated with probiotics to prevent CDI.
6. 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.
7. Subject deprived of liberty by judicial or administrative decision.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02896244 |
| CCMO | NL57769.041.16 |