Cytomegalovirus Disease
Conditions
Keywords
CMV, cytomegalovirus, transplant
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.
Interventions
DRUGValganciclovir
Valcyte per package insert guidelines for 200 days post transplant
BIOLOGICALCMV hyperimmune globulin
100 mg/kg administered at 90 days, 120 days, and 180 days post-transplant
Sponsors
CSL Behring
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Cell Mediated Immunity | 2 years | Positive CMV quantiferon at last follow-up |
| 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 |
| Number of Participants With Acute Cellular and/or Antibody Mediated Rejection | 2 years | — |
| Number of Patients With Early CMV Infection | 100 days | — |
| Number of Participants With Asymptomatic CMV Viremia | 2 years | — |
| Number of Participants With CMV Seroconversions | 2 years | — |
| Number of Participants With Opportunistic Infections | 2 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valcyte - Kidney Transplant Subjects who received a kidney transplant and assigned to the Valcyte only Treatment arm. | 17 |
| Valcyte Then Cytogam - Kidney Transplant Subjects who received a kidney transplant and assigned to the Valcyte then CytogamTreatment arm. | 15 |
| Valcyte - Liver Transplant Subjects who received a liver transplant and assigned to the Valcyte only Treatment arm. | 3 |
| Valcyte Then Cytogam - Liver Transplant Subjects who received a liver transplant and assigned to the Valcyte then Cytogam Treatment arm. | 5 |
| Total | 40 |
Baseline characteristics
| Characteristic | Valcyte - Kidney Transplant | Valcyte Then Cytogam - Kidney Transplant | Valcyte - Liver Transplant | Valcyte Then Cytogam - Liver Transplant | Total |
|---|---|---|---|---|---|
| Age, Continuous | 51 years | 54 years | 58 years | 60 years | 56 years |
| Pre-emptive | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 6 Participants | 0 Participants | 0 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 3 Participants | 5 Participants | 26 Participants |
| Retransplant | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 2 Participants | 0 Participants | 10 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 1 Participants | 5 Participants | 30 Participants |
| Weight (kg) | 71 kg STANDARD_DEVIATION 20 | 88 kg STANDARD_DEVIATION 21 | 84 kg STANDARD_DEVIATION 13 | 91 kg STANDARD_DEVIATION 25 | 84 kg STANDARD_DEVIATION 20 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 20 | 0 / 20 |
| other Total, other adverse events | 16 / 20 | 20 / 20 |
| serious Total, serious adverse events | 4 / 20 | 4 / 20 |
Outcome results
Primary
Number of Patients With Late CMV Disease
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Valcyte | Number of Patients With Late CMV Disease | 0 Participants |
| Valcyte Then Cytogam | Number of Patients With Late CMV Disease | 0 Participants |
Secondary
Number of Participants With Acute Cellular and/or Antibody Mediated Rejection
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Valcyte | Number of Participants With Acute Cellular and/or Antibody Mediated Rejection | 2 Participants |
| Valcyte Then Cytogam | Number of Participants With Acute Cellular and/or Antibody Mediated Rejection | 6 Participants |
Secondary
Number of Participants With Asymptomatic CMV Viremia
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Valcyte | Number of Participants With Asymptomatic CMV Viremia | 1 Participants |
| Valcyte Then Cytogam | Number of Participants With Asymptomatic CMV Viremia | 5 Participants |
Secondary
Number of Participants With CMV Seroconversions
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Valcyte | Number of Participants With CMV Seroconversions | 13 Participants |
| Valcyte Then Cytogam | Number of Participants With CMV Seroconversions | 19 Participants |
Secondary
Number of Participants With Opportunistic Infections
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Valcyte | Number of Participants With Opportunistic Infections | 17 Participants |
| Valcyte Then Cytogam | Number of Participants With Opportunistic Infections | 19 Participants |
Secondary
Number of Patients With Cell Mediated Immunity
Positive CMV quantiferon at last follow-up
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Valcyte | Number of Patients With Cell Mediated Immunity | 8 Participants |
| Valcyte Then Cytogam | Number of Patients With Cell Mediated Immunity | 13 Participants |
Secondary
Number of Patients With Early CMV Infection
Time frame: 100 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Valcyte | Number of Patients With Early CMV Infection | 3 Participants |
| Valcyte Then Cytogam | Number of Patients With Early CMV Infection | 1 Participants |
Secondary
Renal Function
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
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Valcyte | Renal Function | GFR at 180 Days | 57 mL/min/1.73m^2 |
| Valcyte | Renal Function | GFR at 1 year | 59 mL/min/1.73m^2 |
| Valcyte | Renal Function | GFR at 2 years | 59 mL/min/1.73m^2 |
| Valcyte Then Cytogam | Renal Function | GFR at 180 Days | 53 mL/min/1.73m^2 |
| Valcyte Then Cytogam | Renal Function | GFR at 1 year | 54 mL/min/1.73m^2 |
| Valcyte Then Cytogam | Renal Function | GFR at 2 years | 55 mL/min/1.73m^2 |