Cytomegalovirus Infections
Conditions
Brief summary
This study will determine the relative efficacy and safety of up to 100 days Valcyte prophylaxis relative to up to 200 days Valcyte prophylaxis when given for the prevention of CMV disease in high-risk (D+/R-) kidney allograft recipients. The anticipated time on study treatment is 3-12 months and the target sample size is 100-500 individuals.
Interventions
DRUGValganciclovir
900 mg orally daily for up to 100 days
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 16 years of age * CMV seronegative recipient of primary or secondary renal allograft from a living or cadaveric seropositive donor * Adequate hematological and renal function * Patients and partners must agree to maintain effective birth control for 90 days following cessation of study medication
Exclusion criteria
* CMV disease, or receipt of anti-CMV therapy within 30 days prior to screening * Multi-organ transplant recipient * Hepatitis B, hepatitis C or HIV positive * Women who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Developed Cytomegalovirus (CMV) Disease up to Month 12 Post-transplant | 12 months post-transplant | Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 12 months post-transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Developed CMV Disease up to Month 6 Post-transplant | 6 months post-transplant | Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 6 months post-transplant. |
| Percentage of Patients Who Developed CMV Disease up to Month 9 Post-transplant | 9 months post-transplant | Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 9 months post-transplant. |
| Percentage of Patients Who Developed CMV Disease up to Month 18 Post-transplant | 18 months post-transplant | Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 18 months post-transplant. |
| Percentage of Patients Who Developed CMV Disease up to Month 24 Post-transplant | 24 months post-transplant | Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 24 months post-transplant. |
Countries
Australia, Belgium, Brazil, Canada, France, Germany, Italy, New Zealand, Poland, Romania, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valganciclovir up to 100 Days 900 mg valganciclovir orally daily for up to 100 days | 164 |
| Valganciclovir up to 200 Days 900 mg valganciclovir orally daily for up to 200 days | 156 |
| Total | 320 |
Baseline characteristics
| Characteristic | Valganciclovir up to 100 Days | Valganciclovir up to 200 Days | Total |
|---|---|---|---|
| Age, Continuous | 48.5 years STANDARD_DEVIATION 13.76 | 47.0 years STANDARD_DEVIATION 13.51 | 47.8 years STANDARD_DEVIATION 13.64 |
| Sex: Female, Male Female | 45 Participants | 40 Participants | 85 Participants |
| Sex: Female, Male Male | 119 Participants | 116 Participants | 235 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 133 / 164 | 141 / 156 |
| serious Total, serious adverse events | 94 / 164 | 78 / 156 |
Outcome results
Primary
Percentage of Patients Who Developed Cytomegalovirus (CMV) Disease up to Month 12 Post-transplant
Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 12 months post-transplant.
Time frame: 12 months post-transplant
Population: Intent-to-treat population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valganciclovir up to 100 Days | Percentage of Patients Who Developed Cytomegalovirus (CMV) Disease up to Month 12 Post-transplant | 43.6 Percentage of patients |
| Valganciclovir up to 200 Days | Percentage of Patients Who Developed Cytomegalovirus (CMV) Disease up to Month 12 Post-transplant | 23.9 Percentage of patients |
p-value: <=0.000295% CI: [0.25, 0.66]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Who Developed CMV Disease up to Month 18 Post-transplant
Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 18 months post-transplant.
Time frame: 18 months post-transplant
Population: Intent-to-treat population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valganciclovir up to 100 Days | Percentage of Patients Who Developed CMV Disease up to Month 18 Post-transplant | 47.9 Percentage of patients |
| Valganciclovir up to 200 Days | Percentage of Patients Who Developed CMV Disease up to Month 18 Post-transplant | 34.2 Percentage of patients |
p-value: 0.012695% CI: [0.35, 0.88]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Who Developed CMV Disease up to Month 24 Post-transplant
Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 24 months post-transplant.
Time frame: 24 months post-transplant
Population: Intent-to-treat population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valganciclovir up to 100 Days | Percentage of Patients Who Developed CMV Disease up to Month 24 Post-transplant | 48.5 Percentage of patients |
| Valganciclovir up to 200 Days | Percentage of Patients Who Developed CMV Disease up to Month 24 Post-transplant | 34.2 Percentage of patients |
p-value: 0.0195% CI: [0.34, 0.86]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Who Developed CMV Disease up to Month 6 Post-transplant
Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 6 months post-transplant.
Time frame: 6 months post-transplant
Population: Intent-to-treat population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valganciclovir up to 100 Days | Percentage of Patients Who Developed CMV Disease up to Month 6 Post-transplant | 36.2 Percentage of patients |
| Valganciclovir up to 200 Days | Percentage of Patients Who Developed CMV Disease up to Month 6 Post-transplant | 10.3 Percentage of patients |
p-value: <0.000195% CI: [0.11, 0.37]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Who Developed CMV Disease up to Month 9 Post-transplant
Percentage of CMV-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+) who developed CMV disease (confirmed and assumed) within 9 months post-transplant.
Time frame: 9 months post-transplant
Population: Intent-to-treat population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valganciclovir up to 100 Days | Percentage of Patients Who Developed CMV Disease up to Month 9 Post-transplant | 43.6 Percentage of patients |
| Valganciclovir up to 200 Days | Percentage of Patients Who Developed CMV Disease up to Month 9 Post-transplant | 22.6 Percentage of patients |
p-value: 0.000195% CI: [0.22, 0.6]Cochran-Mantel-Haenszel