Immunosuppression
Conditions
Keywords
immunosuppression, steroid withdrawal, rejection, coronary disease, cytomegalovirus infection
Brief summary
This was a study to compare less intense immunosuppression with a more traditional approach. The hypothesis was that less immunosuppression will provide similar protection against rejection than typical 2-3 drug therapy.
Detailed description
This was a prospective, randomized, controlled (open-label) trial of 2 different strategies of immunosuppression in de novo post-heart transplant patients. The hypothesis was that immunosuppression with tacrolimus and mycophenolate mofetil, coupled with rapid steroid weaning would provide similar anti-rejection efficacy as tacrolimus with only a 2 week course of mycophenolate mofetil but including the same rapid steroid wean. The primary endpoint was the mean International Society for Heart and Lung Transplantation (ISHLT) biopsy score over the first 6 months post-transplant. Secondary endpoints included the incidence of adverse events over the first year post-transplant, as well as all-cause mortality, 12 month ISHLT biopsy score (mean), along with the incidence of proven cytomegalovirus disease. In addition, the incidence of allograft vasculopathy as assessed by angiography or intravascular ultrasound was compared between groups.
Interventions
DRUGTacrolimus
tacrolimus
DRUGcombination therapy
MMF
Sponsors
Astellas Pharma Inc
Newark Beth Israel Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult (at least 18 years old) * Undergoing a first heart transplant (no heart/kidney transplants), who receive their transplant at one of the study sites * Specifically INCLUDED are patients on ventricular assist devices, and allosensitized recipients
Exclusion criteria
* Age less than 18 * Inability to provide proper informed consent * Combined organ transplantation * Re-Transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean International Society for Heart and Lung Transplantation Biopsy Score Over the First 6 Months Post-transplantation | 6 months | Mean ISHLT biopsy score Biopsies of the heart may be various grades and each is assigned a numerical score. Grade 0 is 0 points, 1A = 1, 1B = 2, grade 2 = 3, grade 3A = 4, Grade 3B = 5, and grade 4 = 6 units. The mean biopsy score is the numeric average of the biopsy scores for the first 6 post-transplant months. Best value is 0, worst score is 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients Alive at One Year Post-transplant | 1 year | Percent of patients alive at one year post-transplant. In other words, all cause mortality over time |
| Number of Patients With Cytomegalovirus (CMV) at One Year Post-transplant | 1 year | Number of patients developing cytomegalovirus disease by 1 year post-transplant |
| Number of Patients With Allograft Vasculopathy (CAD) at One Year Post Transplant | 1 year | Number of patients diagnosed with allograft vasculopathy / coronary artery disease (CAD) at one year post transplant |
| Mean ISHLT Biopsy Score Over First Year Post-transplant | 1 year | Mean ISHLT biopsy score Biopsies of the heart may be various grades and each is assigned a numerical score. Grade 0 is 0 points, 1A = 1, 1B = 2, grade 2 = 3, grade 3A = 4, Grade 3B = 5, and grade 4 = 6 units. The mean biopsy score is the numeric average of the biopsy scores for the first 6 post-transplant months. Best value is 0, worst score is 6. |
Countries
United States
Participant flow
Recruitment details
Pts recruited from April 2004-Aug 2008
Pre-assignment details
Consent often obtained after transplant
Participants by arm
| Arm | Count |
|---|---|
| Monotherapy These patients will receive tacrolimus, mycophenolate mofetil (MMF) and corticosteroids, followed by a rapid 8 week wean of steroids to discontinuation. MMF will be discontinued in this group at 14 days post-transplant | 79 |
| Combination Therapy These patients will receive tacrolimus, mycophenolate mofetil (MMF) and corticosteroids, followed by a rapid 8 week wean of steroids to discontinuation. MMF will be maintained in this group, unless intolerance develops. | 71 |
| Total | 150 |
Baseline characteristics
| Characteristic | Combination Therapy | Monotherapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 15 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants | 64 Participants | 121 Participants |
| Age, Continuous | 54.6 years STANDARD_DEVIATION 11.6 | 54.7 years STANDARD_DEVIATION 10.7 | 54.65 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 71 participants | 79 participants | 150 participants |
| Sex: Female, Male Female | 11 Participants | 17 Participants | 28 Participants |
| Sex: Female, Male Male | 60 Participants | 62 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 79 | 0 / 71 |
| serious Total, serious adverse events | 2 / 79 | 1 / 71 |
Outcome results
Primary
Mean International Society for Heart and Lung Transplantation Biopsy Score Over the First 6 Months Post-transplantation
Mean ISHLT biopsy score Biopsies of the heart may be various grades and each is assigned a numerical score. Grade 0 is 0 points, 1A = 1, 1B = 2, grade 2 = 3, grade 3A = 4, Grade 3B = 5, and grade 4 = 6 units. The mean biopsy score is the numeric average of the biopsy scores for the first 6 post-transplant months. Best value is 0, worst score is 6.
Time frame: 6 months
Population: all pts, intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean International Society for Heart and Lung Transplantation Biopsy Score Over the First 6 Months Post-transplantation | 0.7 units on a scale | Standard Deviation 0.44 |
| Combination Therapy | Mean International Society for Heart and Lung Transplantation Biopsy Score Over the First 6 Months Post-transplantation | 0.65 units on a scale | Standard Deviation 0.4 |
Secondary
Mean ISHLT Biopsy Score Over First Year Post-transplant
Mean ISHLT biopsy score Biopsies of the heart may be various grades and each is assigned a numerical score. Grade 0 is 0 points, 1A = 1, 1B = 2, grade 2 = 3, grade 3A = 4, Grade 3B = 5, and grade 4 = 6 units. The mean biopsy score is the numeric average of the biopsy scores for the first 6 post-transplant months. Best value is 0, worst score is 6.
Time frame: 1 year
Population: all pts, Intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Monotherapy | Mean ISHLT Biopsy Score Over First Year Post-transplant | 0.67 units on a scale | Standard Deviation 0.39 |
| Combination Therapy | Mean ISHLT Biopsy Score Over First Year Post-transplant | 0.62 units on a scale | Standard Deviation 0.39 |
Comparison: comparing ISHLT biopsy score between groups at 1 yearp-value: 0.44t-test, 2 sided
Secondary
Number of Patients With Allograft Vasculopathy (CAD) at One Year Post Transplant
Number of patients diagnosed with allograft vasculopathy / coronary artery disease (CAD) at one year post transplant
Time frame: 1 year
Population: Percent of patients with allograft CAD at one year post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Number of Patients With Allograft Vasculopathy (CAD) at One Year Post Transplant | 0 patients |
| Combination Therapy | Number of Patients With Allograft Vasculopathy (CAD) at One Year Post Transplant | 0 patients |
Secondary
Number of Patients With Cytomegalovirus (CMV) at One Year Post-transplant
Number of patients developing cytomegalovirus disease by 1 year post-transplant
Time frame: 1 year
Population: all patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Number of Patients With Cytomegalovirus (CMV) at One Year Post-transplant | 2 participants |
| Combination Therapy | Number of Patients With Cytomegalovirus (CMV) at One Year Post-transplant | 2 participants |
Secondary
Percent of Patients Alive at One Year Post-transplant
Percent of patients alive at one year post-transplant. In other words, all cause mortality over time
Time frame: 1 year
Population: all pts, intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Percent of Patients Alive at One Year Post-transplant | 98 percent of participants |
| Combination Therapy | Percent of Patients Alive at One Year Post-transplant | 98 percent of participants |