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

Purpose

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.

Condition	Intervention	Phase
Clostridium Difficile-associated Diarrhea (CDAD)	Drug: intravenous immunoglobulin G (IVIG) Drug: Placebo	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Intravenous Immunoglobulin G Versus Placebo for the Treatment of Patients With Severe Clostridium Difficile-Associated Diarrhea and Colitis

Resource links provided by NLM:

MedlinePlus related topics: Diarrhea

Drug Information available for: Immunoglobulin G Rhophylac

U.S. FDA Resources

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

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).

Secondary Outcome Measures:

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 length of hospital stay.


Enrollment:	14
Study Start Date:	October 2003
Study Completion Date:	April 2008
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: IVIG	Drug: intravenous immunoglobulin G (IVIG) IVIG to be given IV to patients with C-Diff . Other Name: IVIG
Placebo Comparator: Placebo	Drug: Placebo Placebo to be given IV to patients with C-Diff

Detailed Description:

See "Brief Summary" for details

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 -

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00177970

Locations


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

Sponsors and Collaborators

University of Pittsburgh

Shadyside Hospital Foundation

Bayer

Investigators


Principal Investigator:	George L Arnold, MD	University of Pittsburgh

More Information


Responsible Party:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00177970 History of Changes
Other Study ID Numbers:	0311034
Study First Received:	September 13, 2005
Results First Received:	June 15, 2016
Last Updated:	July 28, 2016
Health Authority:	United States: Food and Drug Administration
Individual Participant Data
Plan to Share IPD:	No
Plan Description:	records not available

Additional relevant MeSH terms:


Diarrhea Signs and Symptoms, Digestive Signs and Symptoms Immunoglobulins Antibodies Immunoglobulins, Intravenous	Gamma-Globulins Rho(D) Immune Globulin Immunoglobulin G Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 27, 2016