Back to resultsEvaluation of the Immune Response to Clostridium Difficile in Adults With Clostridium Difficile Infection (CDI)
Primary Purpose
Infections, Clostridium Difficile
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Blood sampling
Stool sample collection
Sponsored by
About this trial
This is an interventional basic science trial for Infections, Clostridium Difficile focused on measuring Serological, Adults, Clostridium difficile, Adult CDI patients
Eligibility Criteria
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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Other
Other
Other
Other
Arm Label
Recurrence group
Sustained response group
Failure to antibiotic Group
Unclassified Group
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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).
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.
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).
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.
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01716533
Brief Title
Evaluation of the Immune Response to Clostridium Difficile in Adults With Clostridium Difficile Infection (CDI)
Official Title
A Serological Study in Adult Subjects With Clostridium Difficile Infection
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
February 2, 2013 (Actual)
Primary Completion Date
June 1, 2015 (Actual)
Study Completion Date
June 1, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infections, Clostridium Difficile
Keywords
Serological, Adults, Clostridium difficile, Adult CDI patients
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
57 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Recurrence group
Arm Type
Other
Arm Description
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.
Arm Title
Sustained response group
Arm Type
Other
Arm Description
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.
Arm Title
Failure to antibiotic Group
Arm Type
Other
Arm Description
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.
Arm Title
Unclassified Group
Arm Type
Other
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Blood sampling
Intervention Description
Blood sampling will be done at Day 0, at Day 14, at recurrence (if applicable) and at end of follow-up.
Intervention Type
Other
Intervention Name(s)
Stool sample collection
Intervention Description
Stool samples will be collected around Day 0, around Day 14 and at recurrence (if applicable).
Primary Outcome Measure Information:
Title
Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 14
Description
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
Title
Serum F2 C-terminal Anti-toxin B Antibody Concentrations
Description
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
Secondary Outcome Measure Information:
Title
Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72
Description
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
Title
Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14
Description
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
Title
Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 0, Within 10 Days After Recurrence and at Day 72
Description
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)
Title
Number of Subjects With Clostridium Difficile Infection (CDI) Recurrence
Description
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
Title
CDI Initial Episodes Severity Characteristics, in All Subjects
Description
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
Title
Number of Subjects With Initial CDI Episode by Severity, in All Subjects
Description
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
Title
Number of Subjects With CDI Recurrence by Severity, in Those Subjects Who Recur
Description
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
Title
Number of Subjects With Failure of Antibiotic Treatment
Description
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
Title
Number of Subjects With Risk Factors Associated With the Initial CDI Episode
Description
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
Title
Number of Subjects With Risk Factors Associated With the CDI Recurrence
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
GSK Investigational Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X5
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Evaluation of the Immune Response to Clostridium Difficile in Adults With Clostridium Difficile Infection (CDI)
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