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

• 1) normalization of WBC's [ Time Frame: during the course of the study ] [ Designated as safety issue: No ]
  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 [ Time Frame: during the course of the study ] [ Designated as safety issue: No ]
  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).

• 1) normalization of WBC’s
• 2) decrease of number of loose stools to <3 per day following treatment

• 1) 75% reduction in abdominal pain/tenderness [ Time Frame: during the course of the study ] [ Designated as safety issue: No ]
  During the course of the study, we expect the IVIG group compared to the placebo group will a 75% reduction in abdominal pain/tenderness
• 2) Quantity of anti-C. difficile antibodies in relationship with recovery of C. difficile diarrhea [ Time Frame: during the course of the study ] [ Designated as safety issue: No ]
  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 [ Time Frame: during the course of the study ] [ Designated as safety issue: No ]
  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. [ Time Frame: during the course of the study ] [ Designated as safety issue: No ]
  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.
• 5) normalization of body temperature during a 24 hour period [ Time Frame: during the course of the study ] [ Designated as safety issue: No ]
  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.
• 6) patients' length of hospital stay [ Time Frame: during the course of the study ] [ Designated as safety issue: No ]
  During the course of the study, we expect the IVIG group compared to the placebo group will have a decrease in lenght of hospital stay.

• 1) Time to improvement of abdominal pain/tenderness
• 2) Quantity of anti-C. difficile antibodies in relationship with recovery of C. difficile diarrhea
• 3) Correlation between antibody responses as measured with ELISA (enzyme immunoassay) and recovery of C. difficile diarrhea
• 4) normalization of neutrophil count on CBC with diff.
• 5) normalization of body temperature during a 24 hour period
• 6) patients’ length of hospital stay

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.

See "Brief Summary" for details

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 -

• Shadyside Hospital Foundation
• Bayer