Cytogam Administration in Abdominal Organ Transplant Recipients at High Risk for Cytomegalovirus Infection

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT01509404
• Collaborator: CSL Behring (Industry)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 49
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the incidence and severity of late Cytomegalovirus (CMV) disease, defined as CMV syndrome or tissue invasive disease occurring between 100 and 200 days and after 200 days post-transplant in patients treated with valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant versus valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Disease	Drug: Valganciclovir; Biological: CMV hyperimmune globulin; Drug: Valganciclovir	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Cytogam Administration in Abdominal Organ Transplant Recipients at High Risk for CMV Infection
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Valcyte valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant	Drug: Valganciclovir; Valcyte per package insert guidelines for 200 days post transplant; Other Names: Valcyte
Active Comparator: Valcyte then Cytogam valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection	Biological: CMV hyperimmune globulin; 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant; Other Names: Cytogam ; Drug: Valganciclovir; valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant; Other Names: Valcyte

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Late CMV Disease [after 200 days post-transplant until 2 years post-transplant]

   Number of any clinically significant late CMV disease, defined as CMV syndrome or tissue-invasive disease occurring after the first 200 days post transplant

Secondary Outcome Measures

1. Number of Patients With Early CMV Infection [100 days]

2. Number of Patients With Cell Mediated Immunity [2 years]

   Positive CMV quantiferon at last follow-up

3. Renal Function [6, 12, and 24 months after transplant]

   Renal function will be assessed by an estimated creatinine clearance utilizing the abbreviated Modification of Diet in Renal Disease (MDRD) equation at 6, 12, and 24 months after transplant

4. Number of Participants With Acute Cellular and/or Antibody Mediated Rejection [2 years]

5. Number of Participants With Opportunistic Infections [2 years]

6. Number of Participants With Asymptomatic CMV Viremia [2 years]

7. Number of Participants With CMV Seroconversions [2 years]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Male and female patients ≥ 18 years of age.

2. Male or female patients who CMV seronegative receiving a kidney, pancreas or liver from a seropositive donor.

3. Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to receiving transplant or study inclusion.

4. The patient has given written informed consent to participate in the study.

Exclusion Criteria:

1. Solid organ transplant recipient is CMV seropositive at the time of transplant.

2. Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV).

3. Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives.

4. Patients with thrombocytopenia (<25,000/mm3 ), with an absolute neutrophil count of < 1,000/mm3); and/or leucopoenia (< 2,000/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion.

5. Patient is taking or has been taking an investigational drug in the 30 days prior to transplant.

6. Patient has a known hypersensitivity to valganciclovir, tacrolimus, mycophenolate mofetil, rabbit anti-thymocyte globulin, CMV hyperimmune globulin, basiliximab or corticosteroids.

7. Patients with severe diarrhea or other gastrointestinal disorders that might interfere with their ability to absorb oral medication.

8. Patient is pregnant or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive human Chorionic Gonadotropin (hCG) laboratory test.

9. Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator.

10. Inability to cooperate or communicate with the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• CSL Behring

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT01509404
• Other Study ID Numbers: Pro00009601
• First Posted: Jan 13, 2012
• Last Update Posted: Oct 4, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Medical University of South Carolina: CMV; cytomegalovirus; transplant
• Additional relevant MeSH terms: Cytomegalovirus Infections; Valganciclovir

Study Results

Participant Flow

Arm/Group Title	Valcyte	Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant	valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
Period Title: Overall Study
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Valcyte - Kidney Transplant	Valcyte Then Cytogam - Kidney Transplant	Valcyte - Liver Transplant	Valcyte Then Cytogam - Liver Transplant	Total
Arm/Group Description	Subjects who received a kidney transplant and assigned to the Valcyte only Treatment arm.	Subjects who received a kidney transplant and assigned to the Valcyte then CytogamTreatment arm.	Subjects who received a liver transplant and assigned to the Valcyte only Treatment arm.	Subjects who received a liver transplant and assigned to the Valcyte then Cytogam Treatment arm.	Total of all reporting groups
Overall Participants	17	15	3	5	40
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	51	54	58	60	56
Sex: Female, Male (Count of Participants)
Female	4 23.5%	4 26.7%	2 66.7%	0 0%	10 25%
Male	13 76.5%	11 73.3%	1 33.3%	5 100%	30 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 5.9%	0 0%	0 0%	0 0%	1 2.5%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	7 41.2%	6 40%	0 0%	0 0%	13 32.5%
White	9 52.9%	9 60%	3 100%	5 100%	26 65%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Retransplant (Count of Participants)
Count of Participants [Participants]	2 11.8%	2 13.3%	0 0%	0 0%	4 10%
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	71 (20)	88 (21)	84 (13)	91 (25)	84 (20)
Pre-emptive (Count of Participants)
Count of Participants [Participants]	3 17.6%	1 6.7%	0 0%	0 0%	4 10%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Late CMV Disease
Description	Number of any clinically significant late CMV disease, defined as CMV syndrome or tissue-invasive disease occurring after the first 200 days post transplant
Time Frame	after 200 days post-transplant until 2 years post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valcyte	Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant	valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
Measure Participants	20	20
Count of Participants [Participants]	0 0%	0 0%

2. Secondary Outcome

Title	Number of Patients With Early CMV Infection
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valcyte	Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant	valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
Measure Participants	20	20
Count of Participants [Participants]	3 17.6%	1 6.7%

3. Secondary Outcome

Title	Number of Patients With Cell Mediated Immunity
Description	Positive CMV quantiferon at last follow-up
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valcyte	Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant	valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
Measure Participants	20	20
Count of Participants [Participants]	8 47.1%	13 86.7%

4. Secondary Outcome

Title	Renal Function
Description	Renal function will be assessed by an estimated creatinine clearance utilizing the abbreviated Modification of Diet in Renal Disease (MDRD) equation at 6, 12, and 24 months after transplant
Time Frame	6, 12, and 24 months after transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valcyte	Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant	valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
Measure Participants	20	20
GFR at 180 Days	57	53
GFR at 1 year	59	54
GFR at 2 years	59	55

5. Secondary Outcome

Title	Number of Participants With Acute Cellular and/or Antibody Mediated Rejection
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valcyte	Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant	valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
Measure Participants	20	20
Count of Participants [Participants]	2 11.8%	6 40%

6. Secondary Outcome

Title	Number of Participants With Opportunistic Infections
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valcyte	Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant	valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
Measure Participants	20	20
Count of Participants [Participants]	17 100%	19 126.7%

7. Secondary Outcome

Title	Number of Participants With Asymptomatic CMV Viremia
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valcyte	Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant	valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
Measure Participants	20	20
Count of Participants [Participants]	1 5.9%	5 33.3%

8. Secondary Outcome

Title	Number of Participants With CMV Seroconversions
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valcyte	Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant	valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
Measure Participants	20	20
Count of Participants [Participants]	13 76.5%	19 126.7%

Adverse Events

Time Frame	up to 2 years
Arm/Group Title	Valcyte		Valcyte Then Cytogam
Arm/Group Description	valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant Valganciclovir: Valcyte per package insert guidelines for 200 days post transplant		valganciclovir per package insert guidelines for 100 days post-transplant with Cytogam 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant for prophylaxis against CMV infection CMV hyperimmune globulin: 100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant Valganciclovir: valganciclovir per package insert guidelines for prophylaxis against CMV infection for 200 days post-transplant
All Cause Mortality
	Valcyte		Valcyte Then Cytogam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		0/20 (0%)
Serious Adverse Events
	Valcyte		Valcyte Then Cytogam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/20 (20%)		4/20 (20%)
Infections and infestations
CMV disease	3/20 (15%)	3	4/20 (20%)	4
Renal and urinary disorders
Graft loss	1/20 (5%)	1	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Valcyte		Valcyte Then Cytogam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/20 (80%)		20/20 (100%)
Blood and lymphatic system disorders
Leukopenia	9/20 (45%)	9	10/20 (50%)	10
Thrombocytopenia	2/20 (10%)	2	1/20 (5%)	1
Infections and infestations
Candidiasis	0/20 (0%)	0	3/20 (15%)	3
Renal and urinary disorders
BK infection	3/20 (15%)	3	5/20 (25%)	5
Acute rejection	2/20 (10%)	2	6/20 (30%)	6

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.