A Phase 3 interventional study of Tacrolimus and Everolimus in Kidney Failure, sponsored by Indiana University. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-05-24.
Sponsored by Indiana University · Phase 3, Interventional, and Prevention
Tacrolimus is the standard immunosuppressive drug used to prevent organ rejection post liver transplant. One side effect of Tacrolimus is nephrotoxicity. Everolimus does not have the nephrotoxicity side effects of Tacrolimus. Replacement of Tacrolimus by Everolimus may have a reduced incidence of renal dysfunction in liver transplant patients who already have chronic kidney disease or peri-operative acute kidney injury. Liver transplant patients receive potent induction immunosuppression in the form of rabbit anti thymocyte globulin. Investigators believe that in conjunction with this induction regimen, patients can be maintained on Everolimus monotherapy without the risk of rejection. Additionally, Everolimus is known to induce tolerance in transplant recipients. Tolerant patients do not require immunosuppression to accept transplant organs. Tacrolimus is a widely used in liver transplant recipients for immunosuppression, however it is associated with nephrotoxicity. Everolimus, on the other hand lacks nephrotoxicity. Whether replacement of tacrolimus by Everolimus preserves kidney function in patients with pre-existing chronic kidney disease or acute kidney injury is not well established. Also, the efficacy and safety of reduced-dose Everolimus with or without Mycophenolate Mofetil in prevention of rejection is unknown.
Primary Aim Assess the effect of Everolimus with or without Mycophenolate Mofetil versus Tacrolimus plus Mycophenolate Mofetil therapy on renal function measured by Glomerular Filtration Rate (GFR). Secondary Aims
Compare the efficacy of Everolimus plus Mycophenolate Mofetil versus Tacrolimus plus Mycophenolate Mofetil therapy as measured by the following:
Following transplant, prior to the one month post transplant visit, subjects will be approached either in the transplant unit in the hospital or at the transplant clinic in the hospital for study participation. Following enrollment, subjects will be randomized at one month post transplant to reduced dose Tacrolimus plus Mycophenolate Mofetil immunosuppression (control group) or to Everolimus plus Mycophenolate Mofetil (study group) maintenance immunosuppression.
After liver transplant, all patients will receive the standard induction regimen and Tacrolimus monotherapy.
INDUCTION:
Rabbit anti-thymocyte globulin (rATG) 1.5 mg/kg of actual body weight rounded to nearest 25 mg and capped at 150 mg for up to three doses given IV on post-operative day (POD) 1, 3, and 5. Some patients may receive only one dose if considered too frail to need all three doses.
30 minutes prior to infusion, pre-medicate with the following: Daily steroid dose Acetaminophen (Tylenol®) 650 mg PO or per NG x 1 dose B - Lay Summary \& Research Design Diphenhydramine (Benadryl®) 25 mg IV push x 1 dose
Steroids:
Methylprednisolone (Solu-Medrol®) 250 mg IV push x 1 dose on POD 1 (given 30 minutes prior to rATG) and 125 mg IV push x 1 dose on POD 3.
Maintenance:
Low dose Tacrolimus (FK / Prograf®) (titrated to a goal trough of 6 ± 1 ng/mL) plus Mycophenolate Mofetil 500 mg BID.
RANDOMIZATION:
On POD 30, patients meeting study criteria will be randomized to either the study arm or control arm. Patients randomized to the study arm will be converted to Everolimus (target trough levels 4-8 ng/mL) plus Mycophenolate Mofetil 500 mg BID therapy. The control arm will be maintained on the low dose Tacrolimus plus Mycophenolate Mofetil therapy.
At 3 months, patients with GFR \<=60 will proceed to reduced dose Everolimus (target trough levels 3-6 ng/mL) plus Mycophenolate Mofetil 500 mg BID therapy. Patients with GFR >60 will proceed to Everolimus monotherapy (target trough levels 4-8 ng/mL).
Complete blood counts, liver function panels, and drug levels will be monitored per Standard of Care [SOC]: initially twice per week for first month, once per week for next two months, once every other week for next three weeks, and then once monthly. Ultrasound, ERCP, biopsy as needed by clinical situation as SOC.
1,995 studies on the registry are indexed under Renal Insufficiency; 173 are open to participants now.
This study's enrollment of 4 is below the median of 43 across 1,504 interventional studies indexed under Renal Insufficiency.
Browse Renal Insufficiency studies →Indiana University is the lead sponsor of 958 studies on the registry; 200 are open to participants now.
Of its 142 completed or terminated interventional studies of FDA-regulated products, 112 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Tacrolimus as maintenance immunosuppression
Drug: Tacrolimus
Everolimus as maintenance immunosuppression
Drug: Everolimus
Low dose Tacrolimus
Also known as: Prograf
Everolimus
Also known as: Zortress
Glomerular Filtration Rate in Patients Treated With Tacrolimus
Glomerular Filtration Rate
Time frame: 36 months post-transplant
Glomerular Filtration Rate in Patients Treated With Everolimus
Glomerular Filtration Rate
Time frame: 36 months post-transplant
Number of Patients Who Experience Transplant Rejection
Biopsy
Time frame: 36 months post-transplant
| Milestone | Control Arm | Study Arm |
|---|---|---|
| Started | 2 | 2 |
| Completed | 0 | 0 |
| Not completed | 2 | 2 |
| Withdrew: Study closure | 2 | 2 |
Glomerular Filtration Rate
No measurements were reported for this outcome.
Glomerular Filtration Rate
No measurements were reported for this outcome.
Biopsy
No measurements were reported for this outcome.
Collected over 6 Months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Control Arm | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) |
| Study Arm | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) |
| Event | Control Arm | Study Arm |
|---|---|---|
| AnemiaBlood and lymphatic system disorders | 0/2 | 1/2 |
| Age, Categorical(Participants) | Control Arm | Study Arm | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 2 | 2 | 4 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(Years) | Control Arm | Study Arm | Total |
|---|---|---|---|
| Mean | 60 (59 to 61) | 61 (58 to 64) | 60.5 (58 to 64) |
| Sex: Female, Male(Participants) | Control Arm | Study Arm | Total |
|---|---|---|---|
| Female | 1 | 1 | 2 |
| Male | 1 | 1 | 2 |
| Race (NIH/OMB)(Participants) | Control Arm | Study Arm | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 2 | 2 | 4 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Control Arm | Study Arm | Total |
|---|---|---|---|
| United States | 2 | 2 | 4 |
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