IVIG Versus Placebo for the Treatment of Patients With Severe C-Diff

Study Overview
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Brief Summary
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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
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See Brief Summary for details

Official Title
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Intravenous Immunoglobulin G Versus Placebo for the Treatment of Patients With Severe Clostridium Difficile-Associated Diarrhea and Colitis

Conditions
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Clostridium Difficile-associated Diarrhea (CDAD)

Intervention / Treatment
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* Drug: intravenous immunoglobulin G (IVIG)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and female greater than 18 years of age Positive stool C. difficile cytotoxin assay and/or biopsy evidence of Pseudomembranous Colitis (PMC) at onset of illness Current history of severe, relapsing CDAD or Current history of severe, refractory CDAD 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) underlying immunosuppression/chronic medical condition altered or depressed mental status as defined by medical chart documentation abdominal pain and/or distention WBC > 20,000 or < 1,500 and/or bandemia > 10% hypoalbuminemia (<3 mg/dL) ascites (clinically or per CT scan findings per medical chart) abnormal CT scan findings per medical chart - Exclusion Criteria: Pregnant or lactating women Selective IgA deficiency Hypersensitivity to immune globulin, human albumin, or thimerosal -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IVIG<br> | Drug: intravenous immunoglobulin G (IVIG)<br>* IVIG to be given IV to patients with C-Diff .<br>* Other names: IVIG;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo to be given IV to patients with C-Diff<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | during the course of the study | 
| 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). | during the course of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | during the course of the study | 
| 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 | during the course of the study | 
| 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. | during the course of the study | 
| 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. | during the course of the study | 
| 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. | during the course of the study | 
| 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. | during the course of the study |