Infections, Clostridium Difficile
Conditions
Keywords
Serological, Adults, Clostridium difficile, Adult CDI patients
Brief summary
This study aims to 1) evaluate the C. difficile-specific immune response in CDI patients and 2) explore the difference in immune response between the patients with CDI recurrence and those with a sustained clinical response.
Detailed description
Patients with an initial episode of CDI will be followed up for CDI recurrence or sustained clinical response. The subjects will be allocated into 2 groups at the study end: * Recurrence Group: Subjects who experience recurrence of CDI after clinical response to antibiotic treatment to treat the initial CDI episode. * Sustained response Group: Subjects who do not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode. This protocol has been amended twice to improve recruitment of subjects in the study.
Interventions
PROCEDUREBlood sampling
Blood sampling will be done at Day 0, at Day 14, at recurrence (if applicable) and at end of follow-up.
Stool samples will be collected around Day 0, around Day 14 and at recurrence (if applicable).
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol or/ and subjects who can receive assistance from his/ her legally acceptable representative (LAR) or a designate who can and will comply with the requirements of the protocol. * A male or female aged 18 years or older at the time of enrolment. * Written informed consent obtained from the subject/ LAR of the subject. * A reasonable prognosis of survival during the study period as judged by the investigator. * Outpatients, emergency room and/ or hospitalized subjects diagnosed with CDI for which the symptoms started maximum 14 days prior to study enrolment. * Subjects who receive or plan to receive antibiotic treatment to treat the CDI episode.
Exclusion criteria
* Concurrently participating or planning to participate in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product. * Previous CDI episode within the previous 6 months before study enrolment (except for up to \ 25% of the subjects). * Chronic diarrheal illness such as, but not limited to, ulcerative colitis or Crohn's disease. * Planned surgery for CDI within 24 hours after study entry. * Previous vaccination against Clostridium difficile. * Having received a Clostridium difficile monoclonal antibody product(s) within the previous 3 months or planned administration during the study period. * Administration of immunoglobulins within the previous 3 months or planned administration during the study period. * Subject having any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the subject participating in the study, would make it unlikely for the subject to complete the study, or would confound the results of the study. * Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within the previous 6 months. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history. * Family history of congenital or hereditary immunodeficiency. * Major congenital defects.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 14 | At Day 14 | Serum anti-toxin B antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), as measured by the Enzyme Linked Immunosorbent Assay (ELISA) for the cut-off of equal to or above (≥) 100 EU/mL. |
| Serum F2 C-terminal Anti-toxin B Antibody Concentrations | At Day 14 | Serum F2 C-terminal anti-toxin B antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), as measured by ELISA for the cut-off of 13.16 EU/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | At Day 0, within 10 days after start of recurrent episode if any, and at end of follow-up (Day 72) | Neutralizing antibody concentrations were expressed as Geometric Mean Titers (GMTs), as measured in an inhibition of cytotoxicity assay (toxin neutralization assays) for the cut-off of 2, expressed in 1/DIL unit, in which DIL is the sample dilution corresponding to 50% neutralization. This measure concerned only diarrhea recurrence. No CDI recurrence was considered as part of the Group Sustained Response. |
| Number of Subjects With Clostridium Difficile Infection (CDI) Recurrence | From Day 0 to Day 72 | A CDI recurrence is defined as the development of a new episode of CDI following clinical response at the end of standard of care (SoC) for the initial CDI episode. |
| CDI Initial Episodes Severity Characteristics, in All Subjects | At Day 0 | Severity characteristics were expressed in duration of days for hospitalization, intensive care unit, Standard of Care (SoC) and CDI episodes. |
| Number of Subjects With Initial CDI Episode by Severity, in All Subjects | At Day 0 | Initial CDI episodes were recorded by severity criteria: medical attention given, admission to intensive care unit, colectomy, death, high white blood cells (WBC) count, high creatinine count, hypotension/shock, clinical response to Standard of Care (SoC). |
| Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72 | At Day 0 and at Day 72 | Serum anti-toxin B antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), as measured by ELISA for the cut-off equal to or above (≥) 100 EU/mL. |
| Number of Subjects With Failure of Antibiotic Treatment | Within 3 months before the initial CDI episodes | Failure of antibiotic treatment against C. difficile is defined as the persistence or the incomplete resolution of symptoms (more than one unformed stool per day) after a full course of antibiotic(s) therapy (minimum 7 days). Aminopen+BetaLactam Inhib,1st Gen.Cephalosporin = Aminopenicillin+Beta-Lactamase Inhibitor and 1st Generation Cephalosporin. Aminopen+BetaLactam Inhib, 3rd Gen.Cephalosporin = Aminopenicillin+Beta-Lactamase Inhibitor and 3rd Generation Cephalosporin excluding Ceftazidime and Fluoroquinolone. Aminopen+BetaLactam Inhib and Fluoroquinolone = Aminopenicillin+Beta-Lactamase Inhibitor and Fluoroquinolone. Antipseudom Pen+BetaLactam Inhib and Cephalosporin = Antipseudomonal Penicillin+Beta-Lactamase Inhibitor and 1st Generation Cephalosporin and 3rd Generation Cephalosporin excluding Ceftazidime and Fluoroquinolone and Glycopeptides (Iv). Antipseudom Pen+BetaLactam Inhib and Glycopeptides = Antipseudomonal Penicillin+Beta-Lactamase Inhibitor and Glycopeptides (Iv). |
| Number of Subjects With Risk Factors Associated With the Initial CDI Episode | At Day 0 | Risk factors for CDI included factors in three main domains involving host factors (advanced age, impaired immune status, co-morbidities); increased exposure to C. difficile spores (longer length of stays, healthcare environment, infected roommates or hand carriage by personnel); and factors that disrupt the normally protective colonic microflora layer (antimicrobials, other medications or procedures). CDI episodes within 6 months: Protocol exclusion criteria for enrolment allowed up to maximum 25% of the planned subjects having a previous CDI episode within the previous 6 months. Antibiotic taken within 3 months: Antibiotic not prescribed to treat C. difficile taken within 3 months before the current CDI episode. |
| Number of Subjects With Risk Factors Associated With the CDI Recurrence | At recurrence (within 10 days of start diarrhea) during a follow up period of up to 72 days per participant | Risk factors for CDI included factors in three main domains involving host factors (advanced age, impaired immune status, co-morbidities); increased exposure to C. difficile spores (longer length of stays, healthcare environment, infected roommates or hand carriage by personnel); and factors that disrupt the normally protective colonic microflora layer (antimicrobials, other medications or procedures). |
| Number of Subjects With CDI Recurrence by Severity, in Those Subjects Who Recur | At recurrence (within 10 days of start diarrhea) during a follow up period of up to 72 days per participant | A CDI recurrence is defined as the development of a new episode of CDI following clinical response at the end of standard of care (SoC) for the initial CDI episode. An episode of diarrhea was not considered as a recurrence of CDI if the stool was negative for C. difficile or if the diarrhea was attributed to another cause than C. difficile. The severity criteria for CDI recurrent episodes were categorized into non-severe and severe. |
| Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14 | At Day 14 | Neutralizing antibody concentrations were expressed as Geometric Mean Titers (GMTs), as measured in an inhibition of cytotoxicity assay (toxin neutralization assays) for the cut-off of 2, expressed in 1/DIL unit, in which DIL is the sample dilution corresponding to 50% neutralization. |
Countries
Canada, United States
Participant flow
Recruitment details
In total 57 subjects were enrolled, among which 11 subjects from one centre in the United States (University of Texas School of Public Health, Houston) who were excluded from final analysis due to GCP issues.
Pre-assignment details
Two extra groups were identified in addition to the two groups foreseen in the protocol: Failure to antibiotic Group and Unclassified Group.
Participants by arm
| Arm | Count |
|---|---|
| Recurrence Group Male or female subjects aged 18 years or older at the time of enrolment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode. | 7 |
| Sustained Response Group Male or female subjects aged 18 years or older at the time of enrolment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode. | 25 |
| Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrolment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode. | 5 |
| Unclassified Group Male or female subjects aged 18 years or older at the time of enrolment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data. | 9 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 2 |
| Overall Study | Failure of antibiotic treatment to treat | 0 | 0 | 5 | 0 |
| Overall Study | Immunosuppressants>14days past 6months | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 5 |
Baseline characteristics
| Characteristic | Recurrence Group | Sustained Response Group | Failure to Antibiotic Group | Unclassified Group | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.1 Years STANDARD_DEVIATION 18.3 | 53.5 Years STANDARD_DEVIATION 20.1 | 58.0 Years STANDARD_DEVIATION 12 | 64.0 Years STANDARD_DEVIATION 18 | 55.1 Years STANDARD_DEVIATION 18.9 |
| Race/Ethnicity, Customized African Heritage / African American | 0 Participants | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unspecified | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White - Caucasian / European Heritage | 7 Participants | 18 Participants | 2 Participants | 4 Participants | 31 Participants |
| Sex: Female, Male Female | 3 Participants | 16 Participants | 2 Participants | 4 Participants | 25 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 3 Participants | 5 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 25 | 0 / 5 | 2 / 9 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 7 | 0 / 25 | 0 / 5 | 0 / 9 |
Outcome results
Primary
Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 14
Serum anti-toxin B antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), as measured by the Enzyme Linked Immunosorbent Assay (ELISA) for the cut-off of equal to or above (≥) 100 EU/mL.
Time frame: At Day 14
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom the result of the considered assay was available for the blood sample taken at Day 14. The development of the serum anti-toxin A ELISA was cancelled, therefore this analysis was not performed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Recurrence Group | Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 14 | 2083.3 EU/mL |
| Sustained Response Group | Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 14 | 3189.4 EU/mL |
| Unclassified Group | Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 14 | 32096.4 EU/mL |
Comparison: ELISA anti-toxin B antibody concentrations at Day 14 were compared between the Sustained response Group and Recurrence Group by using a one-way analysis of variance (ANOVA) model on the log-transformed concentration.p-value: 0.574695% CI: [0.33, 7.14]ANOVA
Primary
Serum F2 C-terminal Anti-toxin B Antibody Concentrations
Serum F2 C-terminal anti-toxin B antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), as measured by ELISA for the cut-off of 13.16 EU/mL.
Time frame: At Day 14
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom the result of the considered assay was available for the blood sample taken at Day 14.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Recurrence Group | Serum F2 C-terminal Anti-toxin B Antibody Concentrations | 149.3 EU/mL |
| Sustained Response Group | Serum F2 C-terminal Anti-toxin B Antibody Concentrations | 246.6 EU/mL |
| Unclassified Group | Serum F2 C-terminal Anti-toxin B Antibody Concentrations | 10736.7 EU/mL |
Comparison: Serum F2 C-terminal anti-toxin B antibody concentrations at Day 14 were compared between the Sustained response Group and Recurrence Group by using a one-way analysis of variance (ANOVA) model on the log-transformed concentration.p-value: 0.712495% CI: [0.1, 26.41]ANOVA
Secondary
CDI Initial Episodes Severity Characteristics, in All Subjects
Severity characteristics were expressed in duration of days for hospitalization, intensive care unit, Standard of Care (SoC) and CDI episodes.
Time frame: At Day 0
Population: The analysis was performed on the Total enrolled cohort, which included all subjects enrolled in the study and who reported any of the characteristics assessed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Recurrence Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of CDI episodes | 10.5 Days |
| Recurrence Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of SoC | 11.0 Days |
| Sustained Response Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of CDI episodes | 6.0 Days |
| Sustained Response Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of hospitalization | 5.0 Days |
| Sustained Response Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of SoC | 14.0 Days |
| Sustained Response Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration in intensive care unit | 5.0 Days |
| Failure to Antibiotic Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of CDI episodes | 24.0 Days |
| Failure to Antibiotic Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of hospitalization | 7.0 Days |
| Failure to Antibiotic Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of SoC | 34.0 Days |
| Unclassified Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration in intensive care unit | 8.0 Days |
| Unclassified Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of hospitalization | 16.0 Days |
| Unclassified Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of SoC | 11.0 Days |
| Unclassified Group | CDI Initial Episodes Severity Characteristics, in All Subjects | Duration of CDI episodes | 10.0 Days |
Secondary
Number of Subjects With CDI Recurrence by Severity, in Those Subjects Who Recur
A CDI recurrence is defined as the development of a new episode of CDI following clinical response at the end of standard of care (SoC) for the initial CDI episode. An episode of diarrhea was not considered as a recurrence of CDI if the stool was negative for C. difficile or if the diarrhea was attributed to another cause than C. difficile. The severity criteria for CDI recurrent episodes were categorized into non-severe and severe.
Time frame: At recurrence (within 10 days of start diarrhea) during a follow up period of up to 72 days per participant
Population: The analysis was performed on the Total enrolled cohort, which included all subjects enrolled in the study who recurred.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recurrence Group | Number of Subjects With CDI Recurrence by Severity, in Those Subjects Who Recur | Non-severe | 7 Participants |
| Recurrence Group | Number of Subjects With CDI Recurrence by Severity, in Those Subjects Who Recur | Severe | 0 Participants |
Secondary
Number of Subjects With Clostridium Difficile Infection (CDI) Recurrence
A CDI recurrence is defined as the development of a new episode of CDI following clinical response at the end of standard of care (SoC) for the initial CDI episode.
Time frame: From Day 0 to Day 72
Population: The analysis was performed on the Total enrolled cohort, which included all subjects enrolled in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recurrence Group | Number of Subjects With Clostridium Difficile Infection (CDI) Recurrence | 7 Participants |
| Sustained Response Group | Number of Subjects With Clostridium Difficile Infection (CDI) Recurrence | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Clostridium Difficile Infection (CDI) Recurrence | 0 Participants |
| Unclassified Group | Number of Subjects With Clostridium Difficile Infection (CDI) Recurrence | 0 Participants |
Secondary
Number of Subjects With Failure of Antibiotic Treatment
Failure of antibiotic treatment against C. difficile is defined as the persistence or the incomplete resolution of symptoms (more than one unformed stool per day) after a full course of antibiotic(s) therapy (minimum 7 days). Aminopen+BetaLactam Inhib,1st Gen.Cephalosporin = Aminopenicillin+Beta-Lactamase Inhibitor and 1st Generation Cephalosporin. Aminopen+BetaLactam Inhib, 3rd Gen.Cephalosporin = Aminopenicillin+Beta-Lactamase Inhibitor and 3rd Generation Cephalosporin excluding Ceftazidime and Fluoroquinolone. Aminopen+BetaLactam Inhib and Fluoroquinolone = Aminopenicillin+Beta-Lactamase Inhibitor and Fluoroquinolone. Antipseudom Pen+BetaLactam Inhib and Cephalosporin = Antipseudomonal Penicillin+Beta-Lactamase Inhibitor and 1st Generation Cephalosporin and 3rd Generation Cephalosporin excluding Ceftazidime and Fluoroquinolone and Glycopeptides (Iv). Antipseudom Pen+BetaLactam Inhib and Glycopeptides = Antipseudomonal Penicillin+Beta-Lactamase Inhibitor and Glycopeptides (Iv).
Time frame: Within 3 months before the initial CDI episodes
Population: The analysis was performed on the Total enrolled cohort, which included all evaluable subjects for whom results about failure of antibiotic treatment (not prescribed to treat Clostridium difficile) were available within 3 months before the initial CDI episodes.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Macrolide | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone And 3rd/4th Gen Fluoroquinolone | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Lincosamide | 2 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone And Lincosamide | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | 1st Generation Cephalosporin | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Glycopeptides (Iv) | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | 4th Generation Cephalosporin and Fluoroquinolone | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Monobactam And Fluoroquinolone | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopenicillin | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib,1st Gen.Cephalosporin | 1 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | 1st Gen Cephalosporin+Tetracyclin, no Tigecyclin | 1 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib, 3rd Gen.Cephalosporin | 1 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Metronidazole and Fluoroquinolone and Lincosamide | 1 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib and Fluoroquinolone | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Subject Does Not Recall Name Of Abx | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopenicillin And Macrolide | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Rifamycin | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Metronidazole and Aminopenicillin | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Antipseudom Pen+BetaLactam Inhib and Cephalosporin | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | 3rd Generation Cephalosporin, no Ceftazidime | 0 Participants |
| Recurrence Group | Number of Subjects With Failure of Antibiotic Treatment | Antipseudom Pen+BetaLactam Inhib and Glycopeptides | 0 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Metronidazole and Aminopenicillin | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib,1st Gen.Cephalosporin | 0 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | 1st Generation Cephalosporin | 2 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Lincosamide | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Antipseudom Pen+BetaLactam Inhib and Cephalosporin | 0 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone And 3rd/4th Gen Fluoroquinolone | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Monobactam And Fluoroquinolone | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopenicillin And Macrolide | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib, 3rd Gen.Cephalosporin | 0 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone And Lincosamide | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | 1st Gen Cephalosporin+Tetracyclin, no Tigecyclin | 0 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Glycopeptides (Iv) | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Antipseudom Pen+BetaLactam Inhib and Glycopeptides | 0 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Macrolide | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | 4th Generation Cephalosporin and Fluoroquinolone | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Subject Does Not Recall Name Of Abx | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib and Fluoroquinolone | 0 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | 3rd Generation Cephalosporin, no Ceftazidime | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopenicillin | 3 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Rifamycin | 1 Participants |
| Sustained Response Group | Number of Subjects With Failure of Antibiotic Treatment | Metronidazole and Fluoroquinolone and Lincosamide | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone And Lincosamide | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | 1st Generation Cephalosporin | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | 1st Gen Cephalosporin+Tetracyclin, no Tigecyclin | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | 3rd Generation Cephalosporin, no Ceftazidime | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | 4th Generation Cephalosporin and Fluoroquinolone | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopenicillin | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib,1st Gen.Cephalosporin | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib, 3rd Gen.Cephalosporin | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib and Fluoroquinolone | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopenicillin And Macrolide | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Antipseudom Pen+BetaLactam Inhib and Cephalosporin | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Antipseudom Pen+BetaLactam Inhib and Glycopeptides | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone And 3rd/4th Gen Fluoroquinolone | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Glycopeptides (Iv) | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Lincosamide | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Macrolide | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Metronidazole and Aminopenicillin | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Metronidazole and Fluoroquinolone and Lincosamide | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Monobactam And Fluoroquinolone | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Rifamycin | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Failure of Antibiotic Treatment | Subject Does Not Recall Name Of Abx | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Antipseudom Pen+BetaLactam Inhib and Cephalosporin | 1 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | 1st Generation Cephalosporin | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Macrolide | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopenicillin And Macrolide | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib and Fluoroquinolone | 1 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Subject Does Not Recall Name Of Abx | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Metronidazole and Aminopenicillin | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib, 3rd Gen.Cephalosporin | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopenicillin | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Rifamycin | 1 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Metronidazole and Fluoroquinolone and Lincosamide | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | 4th Generation Cephalosporin and Fluoroquinolone | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | 3rd Generation Cephalosporin, no Ceftazidime | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Aminopen+BetaLactam Inhib,1st Gen.Cephalosporin | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone And Lincosamide | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Monobactam And Fluoroquinolone | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Glycopeptides (Iv) | 1 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone And 3rd/4th Gen Fluoroquinolone | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Fluoroquinolone | 1 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | 1st Gen Cephalosporin+Tetracyclin, no Tigecyclin | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Lincosamide | 0 Participants |
| Unclassified Group | Number of Subjects With Failure of Antibiotic Treatment | Antipseudom Pen+BetaLactam Inhib and Glycopeptides | 1 Participants |
Secondary
Number of Subjects With Initial CDI Episode by Severity, in All Subjects
Initial CDI episodes were recorded by severity criteria: medical attention given, admission to intensive care unit, colectomy, death, high white blood cells (WBC) count, high creatinine count, hypotension/shock, clinical response to Standard of Care (SoC).
Time frame: At Day 0
Population: The analysis was performed on the Total enrolled cohort, which included all subjects enrolled in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - Unspecified | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Severe CDI episode | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Leukocytosis with high WBC count+Hypotension/shock | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Leukocytosis with high WBC count | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Serum creatinine high level | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Hypotension/shock | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Hospitalization | 2 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Detection of C. difficile strains - No | 6 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Intensive care unit - Yes | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Intensive care unit - No | 7 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Medical personnel visit | 2 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Detection of C. difficile strains - Yes | 1 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Colectomy - Yes | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Colectomy - No | 7 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Medical contact without visit | 1 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - Yes | 6 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Death - Yes | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Stool not collected or discarded - CDI detection | 0 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Death - No | 7 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Emergency Room | 2 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - No | 1 Participants |
| Recurrence Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Non-severe CDI episode | 7 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Colectomy - No | 25 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Leukocytosis with high WBC count+Hypotension/shock | 1 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Intensive care unit - No | 22 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Severe CDI episode | 2 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Emergency Room | 6 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Death - No | 25 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - No | 4 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Leukocytosis with high WBC count | 1 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Medical contact without visit | 1 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Hypotension/shock | 0 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Non-severe CDI episode | 23 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Serum creatinine high level | 0 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Detection of C. difficile strains - No | 23 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Colectomy - Yes | 0 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Medical personnel visit | 3 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Hospitalization | 15 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - Yes | 18 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - Unspecified | 3 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Death - Yes | 0 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Intensive care unit - Yes | 3 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Stool not collected or discarded - CDI detection | 0 Participants |
| Sustained Response Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Detection of C. difficile strains - Yes | 2 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Non-severe CDI episode | 5 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Medical contact without visit | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Medical personnel visit | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Emergency Room | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Hospitalization | 2 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Intensive care unit - Yes | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Intensive care unit - No | 5 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Colectomy - Yes | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Colectomy - No | 5 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Death - Yes | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Death - No | 5 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Severe CDI episode | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Leukocytosis with high WBC count | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Serum creatinine high level | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Hypotension/shock | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Leukocytosis with high WBC count+Hypotension/shock | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - Yes | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - No | 2 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - Unspecified | 3 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Detection of C. difficile strains - Yes | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Detection of C. difficile strains - No | 5 Participants |
| Failure to Antibiotic Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Stool not collected or discarded - CDI detection | 0 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Stool not collected or discarded - CDI detection | 3 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - Yes | 1 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Death - No | 9 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Death - Yes | 0 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Detection of C. difficile strains - No | 5 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - No | 1 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Colectomy - No | 9 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Colectomy - Yes | 0 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Medical personnel visit | 0 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Clinical response at end of SoC - Unspecified | 7 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Intensive care unit - No | 6 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Intensive care unit - Yes | 3 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Medical contact without visit | 0 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Detection of C. difficile strains - Yes | 1 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Serum creatinine high level | 1 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Leukocytosis with high WBC count | 1 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Hospitalization | 8 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Hypotension/shock | 1 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Severe CDI episode | 3 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Non-severe CDI episode | 6 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Medical attention - Emergency Room | 1 Participants |
| Unclassified Group | Number of Subjects With Initial CDI Episode by Severity, in All Subjects | Leukocytosis with high WBC count+Hypotension/shock | 0 Participants |
Secondary
Number of Subjects With Risk Factors Associated With the CDI Recurrence
Risk factors for CDI included factors in three main domains involving host factors (advanced age, impaired immune status, co-morbidities); increased exposure to C. difficile spores (longer length of stays, healthcare environment, infected roommates or hand carriage by personnel); and factors that disrupt the normally protective colonic microflora layer (antimicrobials, other medications or procedures).
Time frame: At recurrence (within 10 days of start diarrhea) during a follow up period of up to 72 days per participant
Population: The analysis was performed on the Total enrolled cohort, which included all subjects enrolled in the study who recurred.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Nutrition via feeding tube during FU period | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Setting of CDI development: Hospital | 1 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Setting of CDI development: Nursing home | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Setting of CDI development: Rehabilitation center | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Setting of CDI development: Community | 6 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Setting of CDI development: Other | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | No admission to hospital during follow-up period | 7 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Admission to hospital during follow-up period | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Not staying in nursing home during FU period | 7 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Staying in nursing home during follow-up period | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Not staying in rehab. center during FU period | 7 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Staying in rehabilitation center during FU period | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | No antibiotic taken during FU period | 5 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Antibiotic taken during FU period | 2 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | No Proton Pump Inhibitors taken during FU period | 4 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Proton Pump Inhibitors taken during FU period | 3 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | No anti-acid drugs taken during FU period | 6 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Anti-acid drugs taken during FU period | 1 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | No nutrition via feeding tube during FU period | 7 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the CDI Recurrence | Setting of CDI development: Rehabilitation center | 0 Participants |
Secondary
Number of Subjects With Risk Factors Associated With the Initial CDI Episode
Risk factors for CDI included factors in three main domains involving host factors (advanced age, impaired immune status, co-morbidities); increased exposure to C. difficile spores (longer length of stays, healthcare environment, infected roommates or hand carriage by personnel); and factors that disrupt the normally protective colonic microflora layer (antimicrobials, other medications or procedures). CDI episodes within 6 months: Protocol exclusion criteria for enrolment allowed up to maximum 25% of the planned subjects having a previous CDI episode within the previous 6 months. Antibiotic taken within 3 months: Antibiotic not prescribed to treat C. difficile taken within 3 months before the current CDI episode.
Time frame: At Day 0
Population: The analysis was performed on the Total enrolled cohort, which included all subjects enrolled in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Community | 5 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Staying in nursing home within 3 months | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Not staying in nursing home within 3 months | 7 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | CDI episodes within 6 months | 1 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Anti-acid drugs taken within 3 months | 4 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Admission to hospital within 3 months | 1 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No admission to hospital within 3 months | 6 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No anti-acid drugs taken within 3 months | 3 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Nursing home | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Nutrition via feeding tube within 3 months | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Proton Pump Inhibitors taken within 3 months | 5 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No proton Pump Inhibitors taken within 3 months | 2 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Rehabilitation center | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No nutrition via feeding tube within 3 months | 7 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Antibiotic taken within 3 months | 6 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No antibiotic taken within 3 months | 1 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Other | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Hospital | 2 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Staying in rehabilitation center within 3 months | 0 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Not staying in rehabilitation center within 3 mths | 7 Participants |
| Recurrence Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No CDI episodes within 6 months | 6 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Community | 18 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Hospital | 6 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Nursing home | 0 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Rehabilitation center | 0 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Other | 1 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No CDI episodes within 6 months | 22 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | CDI episodes within 6 months | 3 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No admission to hospital within 3 months | 15 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Admission to hospital within 3 months | 10 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Not staying in nursing home within 3 months | 25 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Staying in nursing home within 3 months | 0 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Not staying in rehabilitation center within 3 mths | 25 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Staying in rehabilitation center within 3 months | 0 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No antibiotic taken within 3 months | 7 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Antibiotic taken within 3 months | 18 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No proton Pump Inhibitors taken within 3 months | 18 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Proton Pump Inhibitors taken within 3 months | 7 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No anti-acid drugs taken within 3 months | 24 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Anti-acid drugs taken within 3 months | 1 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No nutrition via feeding tube within 3 months | 25 Participants |
| Sustained Response Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Nutrition via feeding tube within 3 months | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Not staying in rehabilitation center within 3 mths | 5 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Nursing home | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No antibiotic taken within 3 months | 3 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Proton Pump Inhibitors taken within 3 months | 5 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Staying in rehabilitation center within 3 months | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Rehabilitation center | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Community | 3 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Nutrition via feeding tube within 3 months | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No anti-acid drugs taken within 3 months | 4 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No admission to hospital within 3 months | 4 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Antibiotic taken within 3 months | 2 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | CDI episodes within 6 months | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Anti-acid drugs taken within 3 months | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Admission to hospital within 3 months | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Other | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No nutrition via feeding tube within 3 months | 5 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Hospital | 1 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Not staying in nursing home within 3 months | 5 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No proton Pump Inhibitors taken within 3 months | 0 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No CDI episodes within 6 months | 4 Participants |
| Failure to Antibiotic Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Staying in nursing home within 3 months | 0 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Nutrition via feeding tube within 3 months | 0 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Staying in nursing home within 3 months | 1 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Other | 1 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Not staying in rehabilitation center within 3 mths | 8 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Anti-acid drugs taken within 3 months | 2 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Staying in rehabilitation center within 3 months | 1 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Rehabilitation center | 0 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Community | 2 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No antibiotic taken within 3 months | 3 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Antibiotic taken within 3 months | 6 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Nursing home | 0 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No proton Pump Inhibitors taken within 3 months | 4 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No nutrition via feeding tube within 3 months | 9 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Proton Pump Inhibitors taken within 3 months | 5 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Setting of CDI development: Hospital | 6 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | CDI episodes within 6 months | 1 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No admission to hospital within 3 months | 4 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No anti-acid drugs taken within 3 months | 7 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Admission to hospital within 3 months | 5 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | No CDI episodes within 6 months | 8 Participants |
| Unclassified Group | Number of Subjects With Risk Factors Associated With the Initial CDI Episode | Not staying in nursing home within 3 months | 8 Participants |
Secondary
Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72
Serum anti-toxin B antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), as measured by ELISA for the cut-off equal to or above (≥) 100 EU/mL.
Time frame: At Day 0 and at Day 72
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom the result of at least one assay was available for the blood sample taken at Day 72. The development of the serum anti-toxin A ELISA was cancelled, therefore this analysis was not performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Recurrence Group | Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72 | Anti-toxin B at Day 0 | 1939.6 EU/mL |
| Recurrence Group | Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72 | Anti-toxin B at Day 72 | 4471.1 EU/mL |
| Sustained Response Group | Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72 | Anti-toxin B at Day 0 | 1682.9 EU/mL |
| Sustained Response Group | Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72 | Anti-toxin B at Day 72 | 3670.4 EU/mL |
| Unclassified Group | Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72 | Anti-toxin B at Day 0 | 19638.5 EU/mL |
| Unclassified Group | Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72 | Anti-toxin B at Day 72 | 64050.6 EU/mL |
Secondary
Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72
Neutralizing antibody concentrations were expressed as Geometric Mean Titers (GMTs), as measured in an inhibition of cytotoxicity assay (toxin neutralization assays) for the cut-off of 2, expressed in 1/DIL unit, in which DIL is the sample dilution corresponding to 50% neutralization. This measure concerned only diarrhea recurrence. No CDI recurrence was considered as part of the Group Sustained Response.
Time frame: At Day 0, within 10 days after start of recurrent episode if any, and at end of follow-up (Day 72)
Population: The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom the result for the considered assay was available for the blood sample taken at the considered time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin A, Day 0 | 14.8 Titer |
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin A, recurrence 1 | 12.2 Titer |
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin A, recurrence 2 | 1.0 Titer |
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin A, Day 72 | 11.1 Titer |
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin B, Day 0 | 3.3 Titer |
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin B, recurrence 1 | 3.0 Titer |
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin B, recurrence 2 | 1.0 Titer |
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin B, Day 72 | 8.0 Titer |
| Sustained Response Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin B, Day 72 | 16.2 Titer |
| Sustained Response Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin B, Day 0 | 9.6 Titer |
| Sustained Response Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin A, Day 0 | 1.5 Titer |
| Sustained Response Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin A, recurrence 1 | 1.0 Titer |
| Sustained Response Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin B, recurrence 1 | 1.0 Titer |
| Sustained Response Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin A, Day 72 | 2.5 Titer |
| Unclassified Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin A, Day 0 | 3.2 Titer |
| Unclassified Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin B, Day 0 | 340.3 Titer |
| Unclassified Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72 | Neutralizing anti-toxin B, Day 72 | 1372.0 Titer |
Secondary
Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14
Neutralizing antibody concentrations were expressed as Geometric Mean Titers (GMTs), as measured in an inhibition of cytotoxicity assay (toxin neutralization assays) for the cut-off of 2, expressed in 1/DIL unit, in which DIL is the sample dilution corresponding to 50% neutralization.
Time frame: At Day 14
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom the result of at least one assay was available for the blood sample taken at Day 14.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14 | Neutralizing anti-toxin A | 11.3 Titer |
| Recurrence Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14 | Neutralizing anti-toxin B | 2.7 Titer |
| Sustained Response Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14 | Neutralizing anti-toxin A | 2.3 Titer |
| Sustained Response Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14 | Neutralizing anti-toxin B | 15.3 Titer |
| Unclassified Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14 | Neutralizing anti-toxin A | 4.7 Titer |
| Unclassified Group | Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14 | Neutralizing anti-toxin B | 1725.7 Titer |