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Relationship Between C. Difficile Toxins' Serum Level With C. Difficile Infection

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ClinicalTrials.gov Identifier: NCT03586206
Recruitment Status : Not yet recruiting
First Posted : July 13, 2018
Last Update Posted : July 13, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Roma Tre University

Brief Summary:
To assess the association between Clostridium difficile (CD) toxins' serum levels and the grade of Clostridium difficile infection (CDI) severity/failure to CDI treatment and rate of recurrence. Furthermore, the kinetics of CD toxins in serum of CDI patients undergoing anti-CDI treatment, as well as the relationship between serum toxins levels and length of CDI diarrhea will be evaluated.

Condition or disease
Clostridium Difficile Clostridium Difficile Infection

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 45 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Relationship Between C. Difficile Toxins' Serum Level With C. Difficile Infection
Estimated Study Start Date : September 15, 2018
Estimated Primary Completion Date : September 15, 2019
Estimated Study Completion Date : December 31, 2020

Group/Cohort
Mild-moderate C.difficile infection
severe C.difficile infection
severe complicated/fulminant C.difficile infection



Primary Outcome Measures :
  1. Setup of the method. [ Time Frame: For each patient, the change of serum toxins levels after 4 and 10 days from the initation of anti-CDI treatment will be compared to levels before initation of anti-CDI treatment. ]
    Mann-Whitney U-tests will be used to compare the intensity of each triplicate chemiluminescent spot of the CDI serum tested with the TcdA and TcdB standard curves, and to compare the intensities of the chemiluminescent spots of CDI patients with those of normal subjects. Quantitative variables will be expressed as the median and IQR.

  2. Validation on the proposed method [ Time Frame: The proposed method will be compared with reference tests evaluating change of serum toxins levels after 4 and 10 days from the initiation of anti-CDI treatment with levels before initiation of anti-CDI treatment. ]
    According to ESCMID guidelines, our method will be compared with reference tests that are defined as the best tests currently available for CDI diagnosis (i.e., cell cytotoxicity neutralization assay (CCNA) and toxigenic culture (TC)). As both these reference tests detect different things, and because of this they will not necessarily agree with each other in all samples, results for each reference test will be analysed separately.

  3. Performance of the proposed method [ Time Frame: The evaluation of the performance of the proposed method will be assed by evaluating the change of toxins levels from baseline levels (time 0) at 4 and 10 days from the initiation of anti-CDI treatment. ]
    The performance of our method will be assessed using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the prediction rule of poor outcome will be calculated. Validity values will be calculated with a 95% CI following an exact binomial distribution. A P value <0.05 will be considered significant

  4. Correlation of toxins kinetics and CDI severity [ Time Frame: Determination of serum toxin kinetics will be evaluated by the change from baseline levels (time 0) at 4 and 10 days from the initiation of anti-CDI treatment. For recurrence rate, the follow up will be of 30 days after cessation of diarrhea. ]
    Toxin kinetics (TcdA alone, TcdB alone, TcdA+TcdB) will be correlated by one-way analysis of variance (ANOVA) with CDI severity (defined according to ESCMID guidelines)

  5. Correlation between toxins levels and the duration of diarrhea [ Time Frame: Determination of serum toxin kinetics will be evaluated by the change from baseline levels (time 0) at 4 and 10 days from the initiation of anti-CDI treatment. ]
    Toxin kinetics (TcdA alone, TcdB alone, TcdA+TcdB) will be correlated with the duration of diarrhea. A multivariate logistic regression model will be used. The odds ratio (OR) and 95% confidence interval (CI) will be calculated. The Spearman correlation coefficients and Wilcoxon rank sum tests will be used to determine whether TcdA and TcdB levels could be associated with the duration of diarrhea.

  6. Correlation between toxins levels and the recurrence rate [ Time Frame: Determination of serum toxin kinetics will be evaluated by the change from baseline levels (time 0) at 30 days from the cessation of diarrhea. ]

    Toxin kinetics (TcdA alone, TcdB alone, TcdA+TcdB) will be correlated with the recurrence rate. A multivariate logistic regression model will be used to assess predictors of poor outcome of CDI. The odds ratio (OR) and 95% confidence interval (CI) will be calculated.

    The Spearman correlation coefficients and Wilcoxon rank sum tests will be used to determine whether TcdA and TcdB levels could be associated with the recurrence rate.


  7. Correlation between toxins levels and mortality rate [ Time Frame: Time-to-Event measure: toxin levels versus mortality rate, from date of patient enrollment to the date of death from any cause assessed up to 12 months. ]
    Survival curves comparing the mortality with toxin(s) levels will be calculated using the Kaplan-Meier method and tested for significance using the log-rank test. P<0.05 will be considered statistically significant.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Primary care clinic
Criteria

Inclusion Criteria:

  • 45 consecutive patients with documented CDI infection, including:
  • 20 with mild-moderate CDI
  • 20 with severe CDI
  • 5 with severe complicated/fulminant CDI, according to ESCMID definition.

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Responsible Party: Roma Tre University
ClinicalTrials.gov Identifier: NCT03586206     History of Changes
Other Study ID Numbers: MISP57289
First Posted: July 13, 2018    Key Record Dates
Last Update Posted: July 13, 2018
Last Verified: May 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Roma Tre University:
Clostridium difficile
toxins
serum
infection

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Clostridium Infections
Gram-Positive Bacterial Infections
Bacterial Infections