Envarsus in Delayed Graft Function (E-DGF) (E-DGF)

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

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.

Study Overview

• Status: Completed
• Conditions: Delayed Graft Function
• Intervention / Treatment: Drug: Tacrolimus; Drug: Envarsus XR

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; Standard of Care Tacrolimus	Drug: Tacrolimus; Tacrolimus (generic; immediate release) is FDA approved for the prophylaxis of organ rejection in heart, kidney and liver transplant recipients.
Experimental: Experimental; Envarsus XR	Drug: Envarsus 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.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 3 months post transplant

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Veloxis Pharmaceuticals
• Investigators: Principal Investigator: Sandesh Parajuli, MBBS, University of Wisconsin School of Medicine and Public Health, Madison

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2019
• Primary Completion (Actual): July 22, 2022
• Study Completion (Actual): July 22, 2022

Study Registration Dates

• First Submitted: March 5, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Kidney Transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Delayed Graft Function; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 2018-0530; A534280 (Other Identifier: UW Madison); SMPH/MEDICINE/NEPHROLOGY (Other Identifier: UW Madison)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes