Clostridium Difficile-associated Diarrhea (CDAD)
Conditions
Brief summary
In this trial, eligible patients will be randomly assigned to receive a single dose of 400 mg/kg of IVIG or a normal saline infusion as placebo over 4-6 hours, in addition to their usual medications for CDAD. We expect to enroll approximately 40 patients over a period of two years from UPMC Shadyside Hospital, McKeesport Hospital, and St. Margaret's Hospital who are unresponsive to standard antimicrobial therapy for CDAD. During the course of this study we expect that IVIG group compared with placebo group will have fewer number of stools per day (\< 3 per day). Secondary endpoints will include normal WBC count, normal body temperature, 75% reduction in abdominal pain / tenderness, and decrease in length of hospital stay. Subjects will sign a written informed consent prior to any study procedures. Patients will be monitored closely during the infusion of the study medication and will continue to be monitored on a daily basis up to the time of discharge. Data collection will include vital signs, CBC, stool C. difficile cytotoxin assay, and stool counts before and after therapy.
Detailed description
See Brief Summary for details
Interventions
DRUGintravenous immunoglobulin G (IVIG)
IVIG to be given IV to patients with C-Diff .
DRUGPlacebo
Placebo to be given IV to patients with C-Diff
Sponsors
Shadyside Hospital Foundation
Bayer
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and female greater than 18 years of age 2. Positive stool C. difficile cytotoxin assay and/or biopsy evidence of Pseudomembranous Colitis (PMC) at onset of illness 3. Current history of severe, relapsing CDAD or Current history of severe, refractory CDAD 4. A score of 6 or 7 on the C.Diff Severity and Prognosis Score (CDSPS) scale27,28,29,30 OR failure to respond (as identified by a score of 4 or more on the CDSPS scale below) to any of the following: a 4-day or more course of oral or IV metronidazole 500 mg po TID or QID; or to a 4-day course of oral vancomycin 125-500 mg po Q6 hours; or to a 4-day course of vancomycin enemas; or failure to respond to a 4-day course of combination therapy of oral vancomycin 125-500 mg po Q6 hours and IV metronidazole 500mg IV Q8 or Q6 hours and/or vancomycin enemas. CDSPS SCALE (each item is scored as one point for a 7 point maximum total) 1. underlying immunosuppression/chronic medical condition 2. altered or depressed mental status as defined by medical chart documentation 3. abdominal pain and/or distention 4. WBC \> 20,000 or \< 1,500 and/or bandemia \> 10% 5. hypoalbuminemia (\<3 mg/dL) 6. ascites (clinically or per CT scan findings per medical chart) 7. abnormal CT scan findings per medical chart -
Exclusion criteria
1. Pregnant or lactating women 2. Selective IgA deficiency 3. Hypersensitivity to immune globulin, human albumin, or thimerosal -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1) Normalization of WBC's | during the course of the study | During the course of the study, we expect the IVIG group compared to the placebo group will have a normal WBC count 3.8-10.0/CMM |
| 2) Decrease of Number of Loose Stools to <3 Per Day Following Treatment | during the course of the study | During the course of the study, we expect the IVIG group compared to the placebo group will have fewer number of stools per day (\<3 per day). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2) Quantity of Anti-C. Difficile Antibodies in Relationship With Recovery of C. Difficile Diarrhea | during the course of the study | The quantity of anti-C. difficile antibodies with improve in relationship with recovery |
| 3) Correlation Between Antibody Responses as Measured With ELISA (Enzyme Immunoassay) and Recovery of C. Difficile Diarrhea | during the course of the study | A correlation will occur between antibody responses as measured with ELISA (enzyme immunoassay) and recovery of C. difficile diarrhea. |
| 4) Normalization of Neutrophil Count on CBC With Diff. | during the course of the study | During the course of the study, we expect the IVIG group compared to the placebo group will have normalization of neutrophil count (1.6-6.7)on CBC with diff. |
| 6) Patients' Length of Hospital Stay | during the course of the study | During the course of the study, we expect the IVIG group compared to the placebo group will have a decrease in length of hospital stay. |
| 5) Normalization of Body Temperature During a 24 Hour Period | during the course of the study | During the course of the study, we expect the IVIG group compared to the placebo group will have a normal body temperature of 98.6 F. |
| 1) 75% Reduction in Abdominal Pain/Tenderness | during the course of the study | During the course of the study, we expect the IVIG group compared to the placebo group will a 75% reduction in abdominal pain/tenderness |
Countries
United States
Participant flow
Recruitment details
Enrollment number retrieved from old IRB database and not from study records and cannot be verified.
Participants by arm
| Arm | Count |
|---|---|
| IVIG intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff . | 0 |
| Placebo Placebo: Placebo to be given IV to patients with C-Diff | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | — Participants |
| Age, Categorical >=65 years | — Participants |
| Age, Categorical Between 18 and 65 years | — Participants |
| Region of Enrollment United States | — participants |
| Sex: Female, Male Female | — Participants |
| Sex: Female, Male Male | — Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
1) Normalization of WBC's
During the course of the study, we expect the IVIG group compared to the placebo group will have a normal WBC count 3.8-10.0/CMM
Time frame: during the course of the study
Population: No results available record destroyed due to age of study. no publications
Primary
2) Decrease of Number of Loose Stools to <3 Per Day Following Treatment
During the course of the study, we expect the IVIG group compared to the placebo group will have fewer number of stools per day (\<3 per day).
Time frame: during the course of the study
Population: No results available record destroyed due to age of study. no publications
Secondary
1) 75% Reduction in Abdominal Pain/Tenderness
During the course of the study, we expect the IVIG group compared to the placebo group will a 75% reduction in abdominal pain/tenderness
Time frame: during the course of the study
Population: No results available record destroyed due to age of study. no publications
Secondary
2) Quantity of Anti-C. Difficile Antibodies in Relationship With Recovery of C. Difficile Diarrhea
The quantity of anti-C. difficile antibodies with improve in relationship with recovery
Time frame: during the course of the study
Population: No results available record destroyed due to age of study. no publications
Secondary
3) Correlation Between Antibody Responses as Measured With ELISA (Enzyme Immunoassay) and Recovery of C. Difficile Diarrhea
A correlation will occur between antibody responses as measured with ELISA (enzyme immunoassay) and recovery of C. difficile diarrhea.
Time frame: during the course of the study
Population: No results available record destroyed due to age of study. no publications
Secondary
4) Normalization of Neutrophil Count on CBC With Diff.
During the course of the study, we expect the IVIG group compared to the placebo group will have normalization of neutrophil count (1.6-6.7)on CBC with diff.
Time frame: during the course of the study
Population: No results available record destroyed due to age of study. no publications
Secondary
5) Normalization of Body Temperature During a 24 Hour Period
During the course of the study, we expect the IVIG group compared to the placebo group will have a normal body temperature of 98.6 F.
Time frame: during the course of the study
Population: No results available record destroyed due to age of study. no publications
Secondary
6) Patients' Length of Hospital Stay
During the course of the study, we expect the IVIG group compared to the placebo group will have a decrease in length of hospital stay.
Time frame: during the course of the study
Population: No results available record destroyed due to age of study. no publications