Infections, Clostridium DifficileNCT01716533
Evaluation of the Immune Response to Clostridium Difficile in Adults With Clostridium Difficile Infection (CDI)
A study testing Blood sampling and Stool sample collection in people with Infections, Clostridium Difficile, run by GlaxoSmithKline at 5 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infections, Clostridium Difficile
- What is being tested?
- Blood sampling and Stool sample collection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 2 Feb 2013to 1 Jun 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States3 sites
GSK Investigational Site
Boston, Massachusetts, 02215
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Little Rock, Arkansas, 72205
Canada2 sites
GSK Investigational Site
Hamilton, Ontario, L8N 4A6
GSK Investigational Site
Toronto, Ontario, M5G 1X5
About this study
Official title: A Serological Study in Adult Subjects With Clostridium Difficile Infection
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.
Read the 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.
- Conditions
- Infections, Clostridium Difficile
- Being tested
- Blood sampling, Stool sample collection
- Keywords
- Serological, Adults, Clostridium difficile, Adult CDI patients
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplingProcedure or surgery
Blood sampling will be done at Day 0, at Day 14, at recurrence (if applicable) and at end of follow-up.
Stool sample collectionOther
Stool samples will be collected around Day 0, around Day 14 and at recurrence (if applicable).
| Study group | Role | What they receive |
|---|---|---|
| Recurrence group | Other | 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. Receives: Procedure: Blood sampling; Other: Stool sample collection |
| Sustained response group | Other | 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. Receives: Procedure: Blood sampling; Other: Stool sample collection |
| Failure to antibiotic Group | Other | 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. Receives: Procedure: Blood sampling; Other: Stool sample collection |
| Unclassified Group | Other | 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. Receives: Procedure: Blood sampling; Other: Stool sample collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: At Day 14
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: At recurrence (within 10 days of start diarrhea) during a follow up period of up to 72 days per participant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2012 (estimated)
- Study start2 Feb 2013
- Primary completion1 Jun 2015
- Study completion1 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Infections, Clostridium DifficileStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01716533
- Sponsor's protocol ID
- 116509
- Status last verified
- Feb 2019
- First submitted
- 18 Oct 2012
- Last updated
- 7 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Serological Study in Adult Subjects With Clostridium Difficile Infection
- ClinicalTrials.gov ID
- NCT01716533
- Acronym / sponsor ID
- 116509
- Conditions
- Infections, Clostridium Difficile
- Keywords
- Serological, Adults, Clostridium difficile, Adult CDI patients
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2013 (actual)
- Primary completion
- 1 Jun 2015 (actual)
- Study completion
- 1 Jun 2015 (actual)
- First posted
- 30 Oct 2012 (estimated)
- Results
- Posted 7 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Recurrence group | Other | Procedure: Blood sampling, Other: Stool sample collectionMale 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. |
| Sustained response group | Other | Procedure: Blood sampling, Other: Stool sample collectionMale 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 | Other | Procedure: Blood sampling, Other: Stool sample collectionMale 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 | Other | Procedure: Blood sampling, Other: Stool sample collectionMale 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood samplingBlood sampling will be done at Day 0, at Day 14, at recurrence (if applicable) and at end of follow-up. | Procedure or surgery | Failure to antibiotic Group, Recurrence group, Sustained response group, Unclassified Group |
| Stool sample collectionStool samples will be collected around Day 0, around Day 14 and at recurrence (if applicable). | Other | Failure to antibiotic Group, Recurrence group, Sustained response group, Unclassified Group |
Primary outcome
Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 14
Time frame: 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
Time frame: 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.
10 secondary outcomes
Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 0 and Day 72
Time frame: At Day 0 and at Day 72
Serum Neutralizing Anti-toxin A and Anti-toxin B Antibody Titers at Day 14
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
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
Time frame: From Day 0 to Day 72
CDI Initial Episodes Severity Characteristics, in All Subjects
Time frame: At Day 0
Number of Subjects With Initial CDI Episode by Severity, in All Subjects
Time frame: At Day 0
Number of Subjects With CDI Recurrence by Severity, in Those Subjects Who Recur
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
Time frame: Within 3 months before the initial CDI episodes
Number of Subjects With Risk Factors Associated With the Initial CDI Episode
Time frame: At Day 0
Number of Subjects With Risk Factors Associated With the CDI Recurrence
Time frame: At recurrence (within 10 days of start diarrhea) during a follow up period of up to 72 days per participant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sampling and Stool sample collection in people with Infections, Clostridium Difficile, run by GlaxoSmithKline at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum Anti-toxin A and Anti-toxin B Antibody Concentrations at Day 14 (time frame: At Day 14). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2019.