Trial Outcomes & Findings for Evaluation of the Immune Response to Clostridium Difficile in Adults With Clostridium Difficile Infection (CDI) (NCT NCT01716533)

Last Updated: 2019-06-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

57 participants

Primary outcome timeframe

At Day 14

Results posted on

2019-06-07

Participant Flow

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.

Two extra groups were identified in addition to the two groups foreseen in the protocol: Failure to antibiotic Group and Unclassified Group.

Participant milestones

Participant milestones
Measure	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.	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.	Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrolment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	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.
Overall Study STARTED	7	25	5	9
Overall Study COMPLETED	7	25	0	1
Overall Study NOT COMPLETED	0	0	5	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrolment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	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.
Overall Study Failure of antibiotic treatment to treat	5	0
Overall Study Withdrawal by Subject	0	5
Overall Study Death	0	2
Overall Study Immunosuppressants>14days past 6months	0	1

Baseline Characteristics

Evaluation of the Immune Response to Clostridium Difficile in Adults With Clostridium Difficile Infection (CDI)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Recurrence Group n=7 Participants 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.	Sustained Response Group n=25 Participants 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.	Failure to Antibiotic Group n=5 Participants 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.	Unclassified Group n=9 Participants 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.	Total n=46 Participants Total of all reporting groups
Age, Continuous	47.1 Years STANDARD_DEVIATION 18.3 • n=39 Participants	53.5 Years STANDARD_DEVIATION 20.1 • n=41 Participants	58.0 Years STANDARD_DEVIATION 12.0 • n=35 Participants	64.0 Years STANDARD_DEVIATION 18.0 • n=31 Participants	55.1 Years STANDARD_DEVIATION 18.9 • n=146 Participants
Sex: Female, Male Female	3 Participants n=39 Participants	16 Participants n=41 Participants	2 Participants n=35 Participants	4 Participants n=31 Participants	25 Participants n=146 Participants
Sex: Female, Male Male	4 Participants n=39 Participants	9 Participants n=41 Participants	3 Participants n=35 Participants	5 Participants n=31 Participants	21 Participants n=146 Participants
Race/Ethnicity, Customized African Heritage / African American	0 Participants n=39 Participants	4 Participants n=41 Participants	3 Participants n=35 Participants	4 Participants n=31 Participants	11 Participants n=146 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	0 Participants n=39 Participants	1 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	1 Participants n=146 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	1 Participants n=31 Participants	1 Participants n=146 Participants
Race/Ethnicity, Customized White - Caucasian / European Heritage	7 Participants n=39 Participants	18 Participants n=41 Participants	2 Participants n=35 Participants	4 Participants n=31 Participants	31 Participants n=146 Participants
Race/Ethnicity, Customized Unspecified	0 Participants n=39 Participants	2 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	2 Participants n=146 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sustained Response Group n=21 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=2 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 14	3189.4 EU/mL Interval 1338.4 to 7600.2	—	32096.4 EU/mL Interval 26.1 to 39518495.0	2083.3 EU/mL Interval 995.8 to 4358.5

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sustained Response Group n=20 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=2 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
Serum F2 C-terminal Anti-toxin B Antibody Concentrations	246.6 EU/mL Interval 52.7 to 1154.8	—	10736.7 EU/mL Interval 1.7 to 69276208.0	149.3 EU/mL Interval 20.2 to 1102.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sustained Response Group n=22 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=2 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
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 Interval 1519.8 to 8864.6	—	64050.6 EU/mL Upper and lower limits were not available as there was only one subject assessed for this time point.	4471.1 EU/mL Interval 1441.1 to 13871.8
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 Interval 858.7 to 3298.2	—	19638.5 EU/mL Interval 217.5 to 1773406.0	1939.6 EU/mL Interval 847.2 to 4440.6

SECONDARY outcome

Timeframe: At Day 14

Outcome measures

Outcome measures
Measure	Sustained Response Group n=22 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=2 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14 Neutralizing anti-toxin A	2.3 Titer Interval 1.2 to 4.5	—	4.7 Titer Interval 0.0 to 1584000000.0	11.3 Titer Interval 0.7 to 194.8
Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14 Neutralizing anti-toxin B	15.3 Titer Interval 4.2 to 55.1	—	1725.7 Titer Interval 125.5 to 23728.0	2.7 Titer Interval 0.4 to 18.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sustained Response Group n=25 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
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 Interval 4.3 to 60.3	—	1372.0 Titer Upper and lower limits were not available as there was only one subject assessed for this time point.	8.0 Titer Interval 1.1 to 56.8
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 Interval 0.9 to 2.4	—	3.2 Titer Interval 0.0 to 7130211.0	14.8 Titer Interval 0.4 to 525.0
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 Upper and lower limits were not available as there was only one subject assessed for this time point.	—	—	12.2 Titer Interval 0.6 to 241.2
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 Upper and lower limits were not available as there was only one subject assessed for this time point.
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 Interval 1.2 to 5.4	—	—	11.1 Titer Interval 0.3 to 422.0
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 Interval 2.7 to 34.1	—	340.3 Titer Interval 0.0 to 461890000.0	3.3 Titer Interval 0.4 to 28.0
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 Upper and lower limits were not available as there was only one subject assessed for this time point.	—	—	3.0 Titer Interval 0.4 to 22.3
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 Upper and lower limits were not available as there was only one subject assessed for this time point.

SECONDARY outcome

Timeframe: From Day 0 to Day 72

Population: The analysis was performed on the Total enrolled cohort, which included all subjects enrolled in the study.

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.

Outcome measures

Outcome measures
Measure	Sustained Response Group n=25 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group n=5 Participants Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=9 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
Number of Subjects With Clostridium Difficile Infection (CDI) Recurrence	0 Participants	0 Participants	0 Participants	7 Participants

SECONDARY outcome

Timeframe: 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.

Severity characteristics were expressed in duration of days for hospitalization, intensive care unit, Standard of Care (SoC) and CDI episodes.

Outcome measures

Outcome measures
Measure	Sustained Response Group n=25 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group n=5 Participants Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=9 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
CDI Initial Episodes Severity Characteristics, in All Subjects Duration of hospitalization	5.0 Days Interval 4.0 to 11.0	7.0 Days Interval 7.0 to 7.0	16.0 Days Interval 8.0 to 22.0	—
CDI Initial Episodes Severity Characteristics, in All Subjects Duration in intensive care unit	5.0 Days Interval 4.0 to 6.0	—	8.0 Days Interval 7.0 to 17.0	—
CDI Initial Episodes Severity Characteristics, in All Subjects Duration of CDI episodes	6.0 Days Interval 4.0 to 13.0	24.0 Days Interval 14.5 to 33.5	10.0 Days Interval 5.0 to 15.0	10.5 Days Interval 9.0 to 15.0
CDI Initial Episodes Severity Characteristics, in All Subjects Duration of SoC	14.0 Days Interval 11.0 to 16.0	34.0 Days Interval 11.0 to 84.0	11.0 Days Interval 10.0 to 26.0	11.0 Days Interval 11.0 to 15.0

SECONDARY outcome

Timeframe: At Day 0

Population: The analysis was performed on the Total enrolled cohort, which included all subjects enrolled in the study.

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).

Outcome measures

Outcome measures
Measure	Sustained Response Group n=25 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group n=5 Participants Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=9 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Stool not collected or discarded - CDI detection	0 Participants	0 Participants	3 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Clinical response at end of SoC - No	4 Participants	2 Participants	1 Participants	1 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Clinical response at end of SoC - Unspecified	3 Participants	3 Participants	7 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Detection of C. difficile strains - Yes	2 Participants	0 Participants	1 Participants	1 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Detection of C. difficile strains - No	23 Participants	5 Participants	5 Participants	6 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Medical attention - Medical contact without visit	1 Participants	1 Participants	0 Participants	1 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Medical attention - Medical personnel visit	3 Participants	1 Participants	0 Participants	2 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Medical attention - Emergency Room	6 Participants	1 Participants	1 Participants	2 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Medical attention - Hospitalization	15 Participants	2 Participants	8 Participants	2 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Intensive care unit - Yes	3 Participants	0 Participants	3 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Intensive care unit - No	22 Participants	5 Participants	6 Participants	7 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Colectomy - Yes	0 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Colectomy - No	25 Participants	5 Participants	9 Participants	7 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Death - Yes	0 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Death - No	25 Participants	5 Participants	9 Participants	7 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Non-severe CDI episode	23 Participants	5 Participants	6 Participants	7 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Severe CDI episode	2 Participants	0 Participants	3 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Leukocytosis with high WBC count	1 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Serum creatinine high level	0 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Hypotension/shock	0 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Leukocytosis with high WBC count+Hypotension/shock	1 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Initial CDI Episode by Severity, in All Subjects Clinical response at end of SoC - Yes	18 Participants	0 Participants	1 Participants	6 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sustained Response Group Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
Number of Subjects With CDI Recurrence by Severity, in Those Subjects Who Recur Non-severe	—	—	—	7 Participants
Number of Subjects With CDI Recurrence by Severity, in Those Subjects Who Recur Severe	—	—	—	0 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Sustained Response Group n=18 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group n=2 Participants Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=6 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=6 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
Number of Subjects With Failure of Antibiotic Treatment 1st Generation Cephalosporin	2 Participants	1 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Aminopenicillin And Macrolide	1 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Antipseudom Pen+BetaLactam Inhib and Cephalosporin	0 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Fluoroquinolone	1 Participants	1 Participants	1 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment 1st Gen Cephalosporin+Tetracyclin, no Tigecyclin	0 Participants	0 Participants	0 Participants	1 Participants
Number of Subjects With Failure of Antibiotic Treatment 3rd Generation Cephalosporin, no Ceftazidime	1 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment 4th Generation Cephalosporin and Fluoroquinolone	1 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Aminopenicillin	3 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Aminopen+BetaLactam Inhib,1st Gen.Cephalosporin	0 Participants	0 Participants	0 Participants	1 Participants
Number of Subjects With Failure of Antibiotic Treatment Aminopen+BetaLactam Inhib, 3rd Gen.Cephalosporin	0 Participants	0 Participants	0 Participants	1 Participants
Number of Subjects With Failure of Antibiotic Treatment Aminopen+BetaLactam Inhib and Fluoroquinolone	0 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Antipseudom Pen+BetaLactam Inhib and Glycopeptides	0 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Fluoroquinolone And 3rd/4th Gen Fluoroquinolone	1 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Fluoroquinolone And Lincosamide	1 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Glycopeptides (Iv)	1 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Lincosamide	1 Participants	0 Participants	0 Participants	2 Participants
Number of Subjects With Failure of Antibiotic Treatment Macrolide	1 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Metronidazole and Aminopenicillin	1 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Metronidazole and Fluoroquinolone and Lincosamide	0 Participants	0 Participants	0 Participants	1 Participants
Number of Subjects With Failure of Antibiotic Treatment Monobactam And Fluoroquinolone	1 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Rifamycin	1 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Failure of Antibiotic Treatment Subject Does Not Recall Name Of Abx	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At Day 0

Population: The analysis was performed on the Total enrolled cohort, which included all subjects enrolled in the study.

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.

Outcome measures

Outcome measures
Measure	Sustained Response Group n=25 Participants Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group n=5 Participants Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group n=9 Participants Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
Number of Subjects With Risk Factors Associated With the Initial CDI Episode No CDI episodes within 6 months	22 Participants	4 Participants	8 Participants	6 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Not staying in rehabilitation center within 3 mths	25 Participants	5 Participants	8 Participants	7 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Proton Pump Inhibitors taken within 3 months	7 Participants	5 Participants	5 Participants	5 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Setting of CDI development: Community	18 Participants	3 Participants	2 Participants	5 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Setting of CDI development: Hospital	6 Participants	1 Participants	6 Participants	2 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Setting of CDI development: Nursing home	0 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Setting of CDI development: Rehabilitation center	0 Participants	0 Participants	0 Participants	0 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Setting of CDI development: Other	1 Participants	1 Participants	1 Participants	0 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode CDI episodes within 6 months	3 Participants	1 Participants	1 Participants	1 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode No admission to hospital within 3 months	15 Participants	4 Participants	4 Participants	6 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Admission to hospital within 3 months	10 Participants	1 Participants	5 Participants	1 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Not staying in nursing home within 3 months	25 Participants	5 Participants	8 Participants	7 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Staying in nursing home within 3 months	0 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Staying in rehabilitation center within 3 months	0 Participants	0 Participants	1 Participants	0 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode No antibiotic taken within 3 months	7 Participants	3 Participants	3 Participants	1 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Antibiotic taken within 3 months	18 Participants	2 Participants	6 Participants	6 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode No proton Pump Inhibitors taken within 3 months	18 Participants	0 Participants	4 Participants	2 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode No anti-acid drugs taken within 3 months	24 Participants	4 Participants	7 Participants	3 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Anti-acid drugs taken within 3 months	1 Participants	1 Participants	2 Participants	4 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode No nutrition via feeding tube within 3 months	25 Participants	5 Participants	9 Participants	7 Participants
Number of Subjects With Risk Factors Associated With the Initial CDI Episode Nutrition via feeding tube within 3 months	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sustained Response Group Male or female subjects aged 18 years or older at the time of enrollment, who did not experience recurrence of CDI after clinical response to the antibiotic treatment to treat the initial CDI episode.	Failure to Antibiotic Group Male or female subjects aged 18 years or older at the time of enrollment, withdrawn due to failure of antibiotic treatment to treat the initial CDI episode.	Unclassified Group Male or female subjects aged 18 years or older at the time of enrollment, who couldn't be classified as sustained response, recurrence, or failure to antibiotic due to missing data.	Recurrence Group n=7 Participants Male or female subjects aged 18 years or older at the time of enrollment, who experienced recurrence of Clostridium difficile infection (CDI) after clinical response to antibiotic treatment to treat the initial CDI episode.
Number of Subjects With Risk Factors Associated With the CDI Recurrence Nutrition via feeding tube during FU period	—	—	—	0 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Setting of CDI development: Community	—	—	—	6 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Setting of CDI development: Hospital	—	—	—	1 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Setting of CDI development: Nursing home	—	—	—	0 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Setting of CDI development: Rehabilitation center	0 Participants	—	—	0 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Setting of CDI development: Other	—	—	—	0 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence No admission to hospital during follow-up period	—	—	—	7 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Admission to hospital during follow-up period	—	—	—	0 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Not staying in nursing home during FU period	—	—	—	7 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Staying in nursing home during follow-up period	—	—	—	0 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Not staying in rehab. center during FU period	—	—	—	7 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Staying in rehabilitation center during FU period	—	—	—	0 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence No antibiotic taken during FU period	—	—	—	5 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Antibiotic taken during FU period	—	—	—	2 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence No Proton Pump Inhibitors taken during FU period	—	—	—	4 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Proton Pump Inhibitors taken during FU period	—	—	—	3 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence No anti-acid drugs taken during FU period	—	—	—	6 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence Anti-acid drugs taken during FU period	—	—	—	1 Participants
Number of Subjects With Risk Factors Associated With the CDI Recurrence No nutrition via feeding tube during FU period	—	—	—	7 Participants

Adverse Events

Recurrence Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sustained Response Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Failure to Antibiotic Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Unclassified Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER