Delayed Graft Function
Conditions
Keywords
Kidney Transplant
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.
Interventions
DRUGEnvarsus XR
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.
DRUGTacrolimus
Tacrolimus (generic; immediate release) is FDA approved for the prophylaxis of organ rejection in heart, kidney and liver transplant recipients.
Sponsors
Veloxis Pharmaceuticals
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent 2. Willing to comply with all study procedures and be available for the duration of the study 3. Male or female, at least 18 years of age 4. Documented diagnosis of DGF or need for dialysis or had dialysis within the first week of kidney transplant 5. Current treatment with tacrolimus based regimen or planned to start tacrolimus based immunosuppressive regimen 6. 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
1. History of hypersensitivity or allergy to any of the study drugs or drugs of similar chemical classes 2. Current use of non-tacrolimus based immunosuppressive regimen or no plan to start tacrolimus based regimen 3. Women who are or plan to become pregnant or breast-feeding during the study period 4. Not suitable for study participation due to other reasons at the discretion of the investigator 5. Major post-surgical complications requiring allograft nephrectomy 6. Multi-organ transplant recipients 7. Non kidney transplant recipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days Needed to Recover From Delayed Graft Function (DGF) | up to 3 months post transplant | The primary endpoint of the study will be the length of time between first dialysis and last dialysis after kidney transplant (duration of DGF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Tacrolimus or Envarsus XR Dose Adjustments Required During the Period of DGF | up to 3 months post transplant | The secondary endpoint will be number of tacrolimus or Envarsus XR dose adjustments required during the period of DGF. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Related Adverse Events | up to 3 months post transplant | Number of participants having adverse event will be reported. Adverse events includes the events such as: infections, malignancies, hematological complications including leukopenia, anemia, and thrombocytopenia, cardiovascular complications and events, neuropathy, tremors, gastrointestinal symptoms, uncontrolled hypertension, serious electrolytes abnormalities and immunosuppression-related adverse effects. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the University of Wisconsin Hospital and Clinics between March 2019 and April 2022.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Tacrolimus (generic; immediate release) is FDA approved for the prophylaxis of organ rejection in heart, kidney and liver transplant recipients. | 50 |
| Experimental 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. | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 2 |
Baseline characteristics
| Characteristic | Standard of Care | Experimental | Total |
|---|---|---|---|
| Age, Customized 30-39 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Customized 40-49 years | 8 Participants | 11 Participants | 19 Participants |
| Age, Customized 50-59 years | 21 Participants | 10 Participants | 31 Participants |
| Age, Customized 60-69 years | 12 Participants | 17 Participants | 29 Participants |
| Age, Customized 70-79 years | 4 Participants | 7 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 45 Participants | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 15 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 29 Participants | 32 Participants | 61 Participants |
| Region of Enrollment United States | 50 Participants | 50 Participants | 100 Participants |
| Sex: Female, Male Female | 19 Participants | 12 Participants | 31 Participants |
| Sex: Female, Male Male | 31 Participants | 38 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 2 / 50 |
| other Total, other adverse events | 50 / 50 | 50 / 50 |
| serious Total, serious adverse events | 23 / 50 | 26 / 50 |
Outcome results
Primary
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).
Time frame: up to 3 months post transplant
Population: 2 patients in SOC and 1 patient in Experimental groups were excluded in analysis due to patients having primary nonfunction of the graft
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Number of Days Needed to Recover From Delayed Graft Function (DGF) | 14.0 days |
| Experimental | Number of Days Needed to Recover From Delayed Graft Function (DGF) | 15.0 days |
Secondary
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.
Time frame: up to 3 months post transplant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care | Number of Tacrolimus or Envarsus XR Dose Adjustments Required During the Period of DGF | 4.0 dose adjustments |
| Experimental | Number of Tacrolimus or Envarsus XR Dose Adjustments Required During the Period of DGF | 3.0 dose adjustments |
Other Pre-specified
Number of Participants Experiencing Related Adverse Events
Number of participants having adverse event will be reported. Adverse events includes the events such as: infections, malignancies, hematological complications including leukopenia, anemia, and thrombocytopenia, cardiovascular complications and events, neuropathy, tremors, gastrointestinal symptoms, uncontrolled hypertension, serious electrolytes abnormalities and immunosuppression-related adverse effects.
Time frame: up to 3 months post transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care | Number of Participants Experiencing Related Adverse Events | 50 Participants |
| Experimental | Number of Participants Experiencing Related Adverse Events | 48 Participants |