Clinical trial NCT00177970: IVIG Versus Placebo for the Treatment of Patients With Severe C-Diff
Official title: Intravenous Immunoglobulin G Versus Placebo for the Treatment of Patients With Severe Clostridium Difficile-Associated Diarrhea and Colitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Clostridium Difficile-associated Diarrhea (CDAD)
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Shadyside Hospital Foundation
name: Bayer
First posted: 2005-09-15
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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 -

Primary outcomes:
measure: 1) Normalization of WBC's
timeFrame: during the course of the study
measure: 2) Decrease of Number of Loose Stools to <3 Per Day Following Treatment
timeFrame: during the course of the study
Secondary outcomes:
measure: 1) 75% Reduction in Abdominal Pain/Tenderness
timeFrame: during the course of the study
measure: 2) Quantity of Anti-C. Difficile Antibodies in Relationship With Recovery of C. Difficile Diarrhea
timeFrame: during the course of the study
measure: 3) Correlation Between Antibody Responses as Measured With ELISA (Enzyme Immunoassay) and Recovery of C. Difficile Diarrhea
timeFrame: during the course of the study
measure: 4) Normalization of Neutrophil Count on CBC With Diff.
timeFrame: during the course of the study
measure: 5) Normalization of Body Temperature During a 24 Hour Period
timeFrame: during the course of the study
measure: 6) Patients' Length of Hospital Stay
timeFrame: during the course of the study
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC McKeesport Hospital and SemperCare Hospital of McKeesport, Inc
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC St. Margaret Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Shadyside Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: George L Arnold, MD
role: PRINCIPAL_INVESTIGATOR
References: