A Phase 4 interventional study of Prograf and Tacrolimus in Renal Transplant Rejection, sponsored by University of California, Los Angeles. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-04-28.
Sponsored by University of California, Los Angeles · Phase 4, Interventional, and Treatment
As the patents for brand-name immunosuppressive medications expire, there is increasing interest in using generic immunosuppressive drugs. However, despite pharmacokinetic studies showing bioequivalence, questions remain regarding the clinical impact of use of generic immunosuppression.
The most important immunosuppressive agent in the modern transplant era is arguably tacrolimus, a calcineurin-inhibitor with a narrow therapeutic index. This study seeks to answer the question regarding the clinical impact of generic tacrolimus use as measured primarily by acute rejection, loss of graft function, and patient death through a randomized trial of 2 phases: Brand tacrolimus only, and Generic A tacrolimus only. Given that kidney transplantations are the most commonly performed transplants with well-defined measures of rejection and graft failure, this organs will be studied in a six-center study designed to accrue the target number of transplant recipients within the one-year study period.
The study has now been branched off into 2 phases. Phase 1: consists of randomization of patients onto brand and generic tacrolimus. This was completed once 40 brand patients were enrolled. Phase 2: consists of patients being enrolled only on generic tacrolimus (standard of care from subject's insurance). This will be completed once there is a total of 160 generic participants. 200 participants total in the study.
A prospective, randomized, open-label, multicenter, parallel, observational study to assess safety and efficacy of 200 kidney transplant recipients comparing brand tacrolimus to generic tacrolimus over a one year follow up period. All subjects will receive other immunosuppressive medications including induction therapy (thymoglobulin, basiliximab, or no induction) and maintenance including mycophenolate mofetil and corticosteroid therapy as directed by standard-of-care at each center. Their medication information will be recorded in their study files.
The study population includes recipients of kidney allografts in the first 14 days after transplantation.
The totals of 7 visits over 12 months period are planned as follows. The blood samples specified below are for the translational research study labs. Subjects will continue to receive routine labs as part of their standard of care from their treating physician. These safety labs are done as part of their stand of care from their treating physician.
If the subject needs more study drug medication before his or her next study visit the subject will come in to the clinic to get a new supply.
First (Baseline) Visit (up to 14 days after transplant but before you are discharged from the hospital):
If you are a woman of child bearing potential, a pregnancy test will be completed prior to the start of the study. If you are pregnant, you cannot participate in this research study. You also cannot participate in this study if you are currently breastfeeding. You must use a medically acceptable method of birth control during the 1-year study period and for 6 weeks after the last dose of study medication.
It is possible that after the study doctor reviews your medical history and test results, he or she may tell you that you do not qualify to be in the study. If you do not qualify for the study, the doctor will tell you the reason(s) why. If you cannot be in this research study, you will not lose any medical benefits, you can still participate in other studies, and you can still receive the standard treatment prescribed by your physician.
After the Baseline Visit, you will have 6 additional study visits. These will be scheduled for 1, 2, 3, 6, 9, and 12 months after your transplant surgery. The following will occur at each visit:
Month 1, 2, 3, 6, and 9 Visits:
Month 12 Visit (End of Study Visit):
If you are Part 1 and require more study medication before your next study visit, you will come in to the clinic to get a new supply. If you are participating in Part 2, you will obtain more study drug from your local pharmacy.
You will continue having your routine blood and urine collections to monitor your kidney function as part of your standard of care treatment at UCLA, UCSD, UCI, and UCD. The schedule for these routine blood and urine collections will depend on your condition and will be at your treating physician's discretion.
Adherence will be measured with daily medication diaries and with the coefficient of variation of tacrolimus in subjects' blood.
University of California, Los Angeles is the lead sponsor of 1,142 studies on the registry; 192 are open to participants now.
Of its 91 completed or terminated interventional studies of FDA-regulated products, 66 (73%) have results posted.
Counted across the registry records on this site, refreshed daily.
WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level > 35 mIU/cc). Women who are using oral, implanted, or injectable contraceptive hormones (intrauterine device), mechanical products or barrier methods (diaphragm, condoms, spermicides), are practicing abstinence, or have a sterile partner (e.g., vasectomy), will be considered of child bearing potential.
In addition, WOCBP who are taking MMF must use methods of birth control as stipulated in the package insert, namely:
Either intrauterine device, or partner with vasectomy, or one hormone (oral contraceptive pill, transdermal patch, vaginal ring, or progesterone injection or implant) and one barrier method (diaphragm or cervical cap with spermicide, contraceptive sponge, or male or female condom), or two barrier methods as described above.
WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) at the time of transplant.
Exclusion Criteria
Arm 1 will receive brand tacrolimus for the entire study
Drug: Prograf
Arm 2 will receive specific generic tacrolimus for the entire study
Drug: Tacrolimus
Brand Drug for the duration of the study.
Generic
Time to First Occurrence of Acute Rejection, Failure, Death
The definition of graft failure includes re-transplant and/or death and, in case of kidney transplant, also includes return to dialysis. Acute rejection was defined as biopsy-proven rejection according to Banff 2007 criteria. Please see the following article for details of the Banff '07 classification: https://www.sciencedirect.com/science/article/pii/S1600613522056428?via%3Dihub.
Time frame: 1 year post-transplant
Number of Participants With Graft Rejection at 1 Year
Rejection was defined as biopsy-proven rejection according to Banff 2007 criteria. Please see the following article for details of the Banff '07 classification: https://www.sciencedirect.com/science/article/pii/S1600613522056428?via%3Dihub.
Time frame: 1 year post-transplant
Number of Participants With Graft Failure at 1 Year
Graft failure as determined by return to dialysis, death, or re-transplant
Time frame: 1 year post-transplant
Number of Participants With Infectious Episodes at 1 Year
Infectious episodes are defined as a positive test result for an infection.
Time frame: 1 year post-transplant
Number of Participants With Malignancy at 1 Year
Malignancy is defined as physician reported malignancy according to review of participants' medical history.
Time frame: 1 year post-transplant
Death or Loss-to-follow-up at 1 Year
Time frame: 1 year post-transplant
Changes in Lymphocyte Subpopulations and Production of Donor Specific HLA Antibodies
Time frame: post-transplant
Number of Participants Who Adhered to Medication Regimen
Patient adherence was assessed by their physician with participants marked as "adherent," "non-adherent," or "unknown."
Time frame: post-transplant
Quality of Life With Medication Regimen
Time frame: post-transplant
Satisfaction With Medication Regimen
Time frame: post-transplant
| Milestone | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| Started | 39 | 132 |
| Completed | 39 | 120 |
| Not completed | 0 | 12 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 4 |
| Withdrew: Tacrolimus discontinued during study | 0 | 6 |
| Withdrew: Other | 0 | 1 |
The definition of graft failure includes re-transplant and/or death and, in case of kidney transplant, also includes return to dialysis. Acute rejection was defined as biopsy-proven rejection according to Banff 2007 criteria. Please see the following article for details of the Banff '07 classification: https://www.sciencedirect.com/science/article/pii/S1600613522056428?via%3Dihub.
| days | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| Time to first of rejection | — | 57.1 ± 66.5 |
| Time to first graft failure | 86 | 200 |
| Time to first death | — | 200 |
Rejection was defined as biopsy-proven rejection according to Banff 2007 criteria. Please see the following article for details of the Banff '07 classification: https://www.sciencedirect.com/science/article/pii/S1600613522056428?via%3Dihub.
| Participants | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| Number of Participants With Graft Rejection at 1 Year | 0 | 9 |
Graft failure as determined by return to dialysis, death, or re-transplant
| Participants | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| Number of Participants With Graft Failure at 1 Year | 1 | 1 |
Infectious episodes are defined as a positive test result for an infection.
| participants | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| Cytomegalovirus infection | 10 | 22 |
| BK virus infection | 3 | 16 |
| Other infection | 15 | 34 |
Malignancy is defined as physician reported malignancy according to review of participants' medical history.
| Participants | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| Number of Participants With Malignancy at 1 Year | 0 | 1 |
| Participants | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| Death or Loss-to-follow-up at 1 Year | 0 | 5 |
No measurements were reported for this outcome.
Patient adherence was assessed by their physician with participants marked as "adherent," "non-adherent," or "unknown."
| Participants | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| Number of Participants Who Adhered to Medication Regimen | 37 | 105 |
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Collected over 1 Year Post-Transplant. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Brand Tacrolimus Only : Prograf | 0/39 (0%) | 19/39 (48.7%) | 32/39 (82.1%) |
| Generic A Only | 1/132 (0.8%) | 43/132 (32.6%) | 105/132 (79.5%) |
| Event | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| Re-hospitalizationGeneral disorders | 13/39 | 41/132 |
| Prolonged hospitalizationGeneral disorders | 10/39 | 6/132 |
| Important medical event requiring medical interventionGeneral disorders | 1/39 | 1/132 |
| Life threatening event associated with an immediate risk of deathGeneral disorders | 0/39 | 1/132 |
| Event | Brand Tacrolimus Only : Prograf | Generic A Only |
|---|---|---|
| InfectionInfections and infestations | 20/39 | 55/132 |
| HypomagnesimiaMetabolism and nutrition disorders | 14/39 | 59/132 |
| HypophosphatemiaMetabolism and nutrition disorders | 12/39 | 51/132 |
| HyperkalemiaMetabolism and nutrition disorders | 14/39 | 41/132 |
| HypercalcemiaMetabolism and nutrition disorders | 13/39 | 20/132 |
| LeukopeniaImmune system disorders | 12/39 | 41/132 |
| Metabolic AcidosisMetabolism and nutrition disorders | 12/39 | 29/132 |
| DiarrheaGastrointestinal disorders | 11/39 | 27/132 |
| AnemiaBlood and lymphatic system disorders | 6/39 | 33/132 |
| Acute Kidney InjuryRenal and urinary disorders | 9/39 | 30/132 |
| Age, Continuous(years) | Brand Tacrolimus Only : Prograf | Generic A Only | Total |
|---|---|---|---|
| Median | 53.0 ± 12.7 | 52.2 ± 13.1 | 52.5 ± 13.0 |
| Sex: Female, Male(Participants) | Brand Tacrolimus Only : Prograf | Generic A Only | Total |
|---|---|---|---|
| Female | 15 | 58 | 73 |
| Male | 24 | 74 | 98 |
| Race/Ethnicity, Customized(Participants) | Brand Tacrolimus Only : Prograf | Generic A Only | Total |
|---|---|---|---|
| White, Non-Hispanic | 9 | 33 | 42 |
| Black | 5 | 12 | 17 |
| Asian | 3 | 12 | 15 |
| Hispanic or Latino | 12 | 50 | 62 |
| Multiracial | 6 | 25 | 31 |
| American Indian or Alaska Native | 4 | 0 | 4 |
| Region of Enrollment(Participants) | Brand Tacrolimus Only : Prograf | Generic A Only | Total |
|---|---|---|---|
| United States | 39 | 132 | 171 |
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