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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
57
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).
GSK Investigational Site
Little Rock, Arkansas, United States
GSK Investigational Site
Boston, Massachusetts, United States
GSK Investigational Site
Houston, Texas, United States
GSK Investigational Site
Hamilton, Ontario, Canada
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
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
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
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
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.
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GSK Investigational Site
Toronto, Ontario, Canada
Time frame: At Day 0, within 10 days after start of recurrent episode if any, and at end of follow-up (Day 72)
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
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
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
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
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
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
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