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

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00177970
• Collaborator: Shadyside Hospital Foundation (Other), Bayer (Industry)
• Enrollment: 14
• Locations: 4
• Arms: 2
• Duration (Months): 54
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Clostridium Difficile-associated Diarrhea (CDAD)	Drug: intravenous immunoglobulin G (IVIG); Drug: Placebo	Phase 4

Detailed Description

See "Brief Summary" for details

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Intravenous Immunoglobulin G Versus Placebo for the Treatment of Patients With Severe Clostridium Difficile-Associated Diarrhea and Colitis
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 1) Normalization of WBC's [during the course of the study]

   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. 2) Decrease of Number of Loose Stools to <3 Per Day Following Treatment [during the course of the study]

   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. 1) 75% Reduction in Abdominal Pain/Tenderness [during the course of the study]

   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. 2) Quantity of Anti-C. Difficile Antibodies in Relationship With Recovery of C. Difficile Diarrhea [during the course of the study]

   The quantity of anti-C. difficile antibodies with improve in relationship with recovery

3. 3) Correlation Between Antibody Responses as Measured With ELISA (Enzyme Immunoassay) and Recovery of C. Difficile Diarrhea [during the course of the study]

   A correlation will occur between antibody responses as measured with ELISA (enzyme immunoassay) and recovery of C. difficile diarrhea.

4. 4) Normalization of Neutrophil Count on CBC With Diff. [during the course of the study]

   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. 5) Normalization of Body Temperature During a 24 Hour Period [during the course of the study]

   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. 6) Patients' Length of Hospital Stay [during the course of the study]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UPMC McKeesport Hospital and SemperCare Hospital of McKeesport, Inc	Pittsburgh	Pennsylvania	United States	15132
2	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania	United States	15213
3	UPMC St. Margaret Hospital	Pittsburgh	Pennsylvania	United States	15215
4	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00177970
• Other Study ID Numbers: 0311034
• First Posted: Sep 15, 2005
• Last Update Posted: Oct 25, 2016
• Last Verified: Sep 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Diarrhea; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; Immunoglobulin G; gamma-Globulins; Rho(D) Immune Globulin

Study Results

Participant Flow

Recruitment Details	Enrollment number retrieved from old IRB database and not from study records and cannot be verified.

Arm/Group Title	IVIG	Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	IVIG	Placebo	Total
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff	Total of all reporting groups
Overall Participants	0	0	0
Age (Count of Participants)
Sex: Female, Male (Count of Participants)
Region of Enrollment (participants) [Number]

Outcome Measures

1. Primary Outcome

Title	1) Normalization of WBC's
Description	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
Time Frame	during the course of the study

Outcome Measure Data

Analysis Population Description

No results available record destroyed due to age of study. no publications

Arm/Group Title	IVIG	Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff
Measure Participants	0	0

2. Primary Outcome

Title	2) Decrease of Number of Loose Stools to <3 Per Day Following Treatment
Description	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).
Time Frame	during the course of the study

Outcome Measure Data

Analysis Population Description

No results available record destroyed due to age of study. no publications

Arm/Group Title	IVIG	Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff
Measure Participants	0	0

3. Secondary Outcome

Title	1) 75% Reduction in Abdominal Pain/Tenderness
Description	During the course of the study, we expect the IVIG group compared to the placebo group will a 75% reduction in abdominal pain/tenderness
Time Frame	during the course of the study

Outcome Measure Data

Analysis Population Description

No results available record destroyed due to age of study. no publications

Arm/Group Title	IVIG	Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff
Measure Participants	0	0

4. Secondary Outcome

Title	2) Quantity of Anti-C. Difficile Antibodies in Relationship With Recovery of C. Difficile Diarrhea
Description	The quantity of anti-C. difficile antibodies with improve in relationship with recovery
Time Frame	during the course of the study

Outcome Measure Data

Analysis Population Description

No results available record destroyed due to age of study. no publications

Arm/Group Title	IVIG	Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff
Measure Participants	0	0

5. Secondary Outcome

Title	3) Correlation Between Antibody Responses as Measured With ELISA (Enzyme Immunoassay) and Recovery of C. Difficile Diarrhea
Description	A correlation will occur between antibody responses as measured with ELISA (enzyme immunoassay) and recovery of C. difficile diarrhea.
Time Frame	during the course of the study

Outcome Measure Data

Analysis Population Description

No results available record destroyed due to age of study. no publications

Arm/Group Title	IVIG	Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff
Measure Participants	0	0

6. Secondary Outcome

Title	4) Normalization of Neutrophil Count on CBC With Diff.
Description	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.
Time Frame	during the course of the study

Outcome Measure Data

Analysis Population Description

No results available record destroyed due to age of study. no publications

Arm/Group Title	IVIG	Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff
Measure Participants	0	0

7. Secondary Outcome

Title	5) Normalization of Body Temperature During a 24 Hour Period
Description	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.
Time Frame	during the course of the study

Outcome Measure Data

Analysis Population Description

No results available record destroyed due to age of study. no publications

Arm/Group Title	IVIG	Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff
Measure Participants	0	0

8. Secondary Outcome

Title	6) Patients' Length of Hospital Stay
Description	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.
Time Frame	during the course of the study

Outcome Measure Data

Analysis Population Description

No results available record destroyed due to age of study. no publications

Arm/Group Title	IVIG	Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .	Placebo: Placebo to be given IV to patients with C-Diff
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	No results available. Records were destroyed due to age of study.
Arm/Group Title	IVIG		Placebo
Arm/Group Description	intravenous immunoglobulin G (IVIG): IVIG to be given IV to patients with C-Diff .		Placebo: Placebo to be given IV to patients with C-Diff
All Cause Mortality
	IVIG		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IVIG		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	IVIG		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.