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

Clostridium Difficile-associated Diarrhea (CDAD) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00177970
• Other study ID #: 0311034
• Status: Terminated
• Phase: Phase 4
• First received: September 13, 2005
• Last updated: November 30, 2015
• Start date: October 2003
• Est. completion date: April 2008

Study information

• Verified date: November 2015
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

See "Brief Summary" for details

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Clostridium Difficile-associated Diarrhea (CDAD)
• Diarrhea

Intervention

Drug:
• intravenous immunoglobulin G (IVIG)
IVIG to be given IV to patients with C-Diff vs placebo.

Locations

Country	Name	City	State
United States	UPMC McKeesport Hospital and SemperCare Hospital of McKeesport, Inc	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	UPMC Shadyside Hospital	Pittsburgh	Pennsylvania
United States	UPMC St. Margaret Hospital	Pittsburgh	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
University of Pittsburgh	Bayer, Shadyside Hospital Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	during the course of the study	No
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).	during the course of the study	No
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	during the course of the study	No
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	during the course of the study	No
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.	during the course of the study	No
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.	during the course of the study	No
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.	during the course of the study	No
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.	during the course of the study	No