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

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

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.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile-associated Diarrhea (CDAD)
• Intervention / Treatment: Drug: intravenous immunoglobulin G (IVIG); Drug: Placebo

Detailed Description

See "Brief Summary" for details

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Shadyside Hospital
    • Pittsburgh, Pennsylvania, United States, 15132
      • UPMC McKeesport Hospital and SemperCare Hospital of McKeesport, Inc
    • Pittsburgh, Pennsylvania, United States, 15215
      • UPMC St. Margaret Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 -

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: Bayer; Shadyside Hospital Foundation
• Investigators: Principal Investigator: George L Arnold, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Estimate): October 25, 2016
• Last Update Submitted That Met QC Criteria: September 14, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin; Immunoglobulin G
• Other Study ID Numbers: 0311034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: records not available