Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant Recipients

With the availability of well-studied once-daily formulations of tacrolimus, the ability to achieve a true once-daily immunosuppressant regimen along with everolimus and steroids may finally be achievable and have the potential to optimize immunosuppression safety and efficacy in kidney transplantation.

Study Overview

• Status: Completed
• Conditions: Immunosuppression
• Intervention / Treatment: Drug: Tacrolimus; Drug: Prednisone; Drug: Mycophenolate mofetil; Drug: Everolimus

Detailed Description

A once-daily immunosuppressant regimen comprising of Envarsus-everolimus-prednisone will have 6-month treatment failure rates that are non-inferior to the twice-daily regimen of Envarsus-mycophenolate mofetil-prednisone and will have improved patient-reported adherence.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

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

Description

1. Inclusion criteria

1. Male or female adult (≥18 years old) with a history of solitary kidney transplant within 3 months (±2 months) of transplant with self-reported medication adherence issues, as indicated by a MMAS-8 of at least 1.
2. Patients must be capable of understanding the purposes and risks of the study and have the ability to give written informed consent and be willing to participate and comply with the study.
3. Women of childbearing potential must have a negative pregnancy test within the 48 hours prior to receiving study medication.
4. Women of childbearing potential and sexually active males must be willing to use contraception, as indicated in Section 6 of the protocol. Subjects who are not of reproductive potential (status post bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or vasectomy), not sexually active, whose current partner(s) is not of reproductive potential, or whose sexual activity is exclusively homosexual are eligible without requiring the use of contraception.

2. Exclusion criteria

1. Patients will be excluded if they are pregnant or nursing females or males with a pregnant female partner
2. Recipient of multiple organ transplant
3. Recipient of a non-renal organ
4. Proteinuria > 800 mg/24 hour
5. eGFR < 30 ml/min
6. WBC ≤ 2k/mm3
7. Plt ≤ 50k/mm3
8. Triglycerides > 500 mg/dL
9. HIV positive (HIV ab +)
10. Unable to tolerate oral medications
11. Use of another investigational product within thirty days prior to receiving study medication
12. Acute graft rejection within the past month (Banff 1A or higher) or received an ABO incompatible donor organ.
13. A condition or disorder that, in the opinion of the investigator, may adversely affect the outcome of the study or the safety of the subject

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: Tacrolimus + MMF; Tacrolimus IR BID (5-12ng/mL) + mycophenolate mofetil 1g BID + prednisone x at least 3 months, then converted to Tacrolimus Daily (5 -12ng/mL) + mycophenolate mofetil 1g BID + prednisone x 6 months	Drug: Tacrolimus; goal trough level 5-12ng/mL; Other Names: Envarsus; Drug: Prednisone; goal dose 5mg QD; Other Names: Corticosteroids; Methylprednisolone; Drug: Mycophenolate mofetil; goal dose 1g BID
Active Comparator: Envarsus + Everolimus; Tacrolimus IR BID (5-12ng/mL) + mycophenolate mofetil 1g BID + prednisone x at least 3 months, then converted to Envarsus Daily (2-5ng/mL) + Everolimus Daily (3-8ng/mL) + prednisone x 6 months	Drug: Tacrolimus; goal trough level 5-12ng/mL; Other Names: Envarsus; Drug: Prednisone; goal dose 5mg QD; Other Names: Corticosteroids; Methylprednisolone; Drug: Everolimus; goal trough level 3-8ng/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported Medication Adherence From Baseline to 6 Months.	Percent of subjects reporting high medication adherence at baseline compared to 6 months post-conversion, using the Morisky Medication Adherence scale (MMAS). The MMAS rates medication adherence on a scale of 0 to 8. 0 is high adherence, 1-2 is medium adherence, and greater than or equal to 3 is low adherence.	6 months post conversion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants Experiencing Acute Allograft Rejection	Estimate the composite of treatment failure rate, defined as acute allograft rejection with a Banff grade 1A or higher, graft loss, or death at six months post-conversion, in patients converted to a once-daily immunosuppressant regimen of Envarsus®, everolimus, and prednisone versus patients converted to a twice-daily regimen of Envarsus®, MMF, and prednisone.	Baseline to 6 months post conversion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject Specific Change on Medication Side Effect Scale	Examine subject specific change on a validated Medication Side Effect Scale at the time of the conversion versus six months post-conversion, compared between the two arms. Side effect burden scale is from 0 to 180. A lower score is less side effect burden, a higher score is more side effect burden.	Baseline to 6 months post conversion
Percent of Participants Who Experienced Kidney Transplant Graft Loss	Measure and compare time-to-event analysis between the two arms graft loss (time to event analysis)	Baseline to 6 months post conversion

Collaborators and Investigators

• Sponsor: Medical University of South Carolina

Publications and helpful links

General Publications

• Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 12;9(9):CD012854. doi: 10.1002/14651858.CD012854.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): December 27, 2018
• Study Completion (Actual): December 27, 2018

Study Registration Dates

• First Submitted: October 13, 2016
• First Submitted That Met QC Criteria: November 1, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): December 24, 2019
• Last Update Submitted That Met QC Criteria: December 9, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Methylprednisolone; Prednisone; Tacrolimus; Mycophenolic Acid; Everolimus
• Other Study ID Numbers: Pro00059602