Envarsus in Delayed Graft Function (E-DGF)

Study Overview
=================
Brief Summary
-----------------
Envarsus XR is an extended release tacrolimus designed to deliver tacrolimus more consistently, thus avoiding large fluctuations of tacrolimus trough levels with Envarsus XR compared to immediate release tacrolimus. It is expected that patients with DGF on Envarsus XR will have more stable tacrolimus levels and facilitate early recover from DGF compared to immediate release tacrolimus.

Detailed Description
-----------------
This is a single center randomized phase IV trial of comparing extended release Envarsus XR (study drug) once a day vs immediate release tacrolimus twice a day in a new kidney transplant recipients with delayed graft function (DGF). The primary study endpoint is the interval between first dialysis and last dialysis after kidney transplant (duration of DGF). The second end point is the number of tacrolimus or Envarsus XR dose adjustments required during the period of DGF.

Official Title
-----------------
Envarsus in Delayed Graft Function: A Phase IV, Randomized, Single Center Study Among Kidney Transplant Recipients With Delayed Graft Function (DGF) to Study the Effect of Envarsus XR in the DGF Recovery

Conditions
-----------------
Delayed Graft Function

Intervention / Treatment
-----------------
* Drug: Envarsus XR
* Drug: Tacrolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing and able to provide written informed consent Willing to comply with all study procedures and be available for the duration of the study Male or female, at least 18 years of age Documented diagnosis of DGF or need for dialysis or had dialysis within the first week of kidney transplant Current treatment with tacrolimus based regimen or planned to start tacrolimus based immunosuppressive regimen Females of childbearing potential must have a negative urine or serum pregnancy test prior to randomization and agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to randomization, for the duration of study participation, and for 7 days following completion of therapy. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Exclusion Criteria: History of hypersensitivity or allergy to any of the study drugs or drugs of similar chemical classes Current use of non-tacrolimus based immunosuppressive regimen or no plan to start tacrolimus based regimen Women who are or plan to become pregnant or breast-feeding during the study period Not suitable for study participation due to other reasons at the discretion of the investigator Major post-surgical complications requiring allograft nephrectomy Multi-organ transplant recipients Non kidney transplant recipients

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Standard of Care Tacrolimus | Drug: Tacrolimus<br>* Tacrolimus (generic; immediate release) is FDA approved for the prophylaxis of organ rejection in heart, kidney and liver transplant recipients.<br>|
| Experimental: Experimental<br>Envarsus XR | Drug: Envarsus XR<br>* Envarsus XR is FDA approved for the prophylaxis of organ rejection in kidney transplant recipients converted from tacrolimus immediate-release formulations, in combination with other immunosuppressants. Envarsus XR, is designed to deliver tacrolimus more smoothly over the whole day. Envarsus XR, a calcineurin-inhibitor immunosuppressant, is available for oral administration as extended-release tablets containing the equivalent of 0.75 mg, 1 mg, or 4 mg of anhydrous tacrolimus USP. Inactive ingredients include hypromellose USP, lactose monohydrate NF, polyethylene glycol NF, poloxamer NF, magnesium stearate NF, tartaric acid NF, butylated hydroxytoluene NF, and dimethicone NF. Tacrolimus is the active ingredient in ENVARSUS XR.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days Needed to Recover From Delayed Graft Function (DGF) | The primary endpoint of the study will be the length of time between first dialysis and last dialysis after kidney transplant (duration of DGF). | up to 3 months post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Tacrolimus or Envarsus XR Dose Adjustments Required During the Period of DGF | The secondary endpoint will be number of tacrolimus or Envarsus XR dose adjustments required during the period of DGF. | up to 3 months post transplant | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Kidney Transplant