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

NCT03586206 | Unknown DMC

• 1 other identifier: MISP57289
• Study Type: observational
• Target: 45
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Clostridium Difficile; Clostridium Difficile Infection

Keywords

Clostridium difficile; toxins; serum; infection

Outcome Measures

Primary Outcomes (7)

• Setup of the method.

  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.

  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.

• Validation on the proposed method

  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.

  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.

• Performance of the proposed method

  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

  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.

• Correlation of toxins kinetics and CDI severity

  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)

  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.

• Correlation between toxins levels and the duration of diarrhea

  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.

  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.

• Correlation between toxins levels and the recurrence rate

  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.

  Determination of serum toxin kinetics will be evaluated by the change from baseline levels (time 0) at 30 days from the cessation of diarrhea.

• Correlation between toxins levels and mortality rate

  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.

  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.

Study Arms (3)

Mild-moderate C.difficile infection

severe C.difficile infection

severe complicated/fulminant C.difficile infection

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Primary care clinic

You may qualify if:

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

Sponsors & Collaborators

• Roma Tre University: lead
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Conditions

Clostridium Infections; Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2018
• First Posted: July 13, 2018
• Study Start: September 15, 2018
• Primary Completion: September 15, 2019
• Study Completion: December 31, 2020
• Last Updated: July 13, 2018

Record last verified: 2018-05