Envarsus XL Immunosuppression Following Liver Transplantation

NCT03828058 | Completed Phase 2 FDA Drug

• 1 other identifier: 18-05876-FB
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

The standard immunosuppressive regimen for liver transplantation includes twice daily tacrolimus (Prograf). In other transplantation models, there are potential benefits to extended release formulations as lower peak concentrations are thought to have lower rates of nephrotoxicity. Additionally, compliance with once daily medications is felt to be easier than twice daily medications. Our aim is to look at our prospective liver transplant group and see if once daily tacrolimus (Envarsus XR) results in improved renal function as well as improved health care quality of life.

Conditions

Recipients of Liver Transplant

Outcome Measures

Primary Outcomes (1)

• Change in estimated glomerular filtration rate (eGFR) over the first year after liver transplant

  We will be assessing differences in renal function based on calculated eGFR by MDRD6 equation.

  3, 6, and 12 months post-transplant

Secondary Outcomes (1)

• Quality of Life Assessment

  3, 6, and 12 months post-transplant

Study Arms (2)

Envarsus XR

EXPERIMENTAL

Envarsus XR orally administered Daily

Drug: Envarsus XR

Prograf

ACTIVE COMPARATOR

Prograf PO administered twice daily Generic Name: tacrolimus Dosage of prograf will be determined by trough levels and adjusted accordingly

Drug: Prograf

Interventions

Envarsus XR DRUG

Envarsus XR to be administered orally, once a day. Dosage will be adjusted as determined by trough blood levels.

Also known as: ENVARSUS XR 0.75Mg Extended-Release Tablet, ENVARSUS XR 1Mg Extended-Release Tablet, ENVARSUS XR 4Mg Extended-Release Tablet

Envarsus XR

Prograf DRUG

Prograf 2 mg BID to be administered orally, twice a day. Dosage will be adjusted as determined by trough blood levels.

Also known as: Tacrolimus

Prograf

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 years or older
• Recipients of a first-time liver transplant
• Serum Creatinine level less than 2.0 on Post-Operative Day 3-7
• Ability to take oral medication and be willing to adhere to the assigned immunosuppression regimen
• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration

You may not qualify if:

• Any prior use of tacrolimus or cyclosporine
• Recipients of prior organ transplant
• Need for hemodialysis in the week preceding or following liver transplantation
• Recipients of living donor liver or split deceased donor liver allografts
• Recipients of combined liver/kidney transplants
• Pregnancy or lactation
• Recipients of ABO incompatible liver allografts

Sponsors & Collaborators

• Methodist Healthcare: lead

Study Sites (1)

Methodist Healthcare, University Hospital

Memphis, Tennessee, 38104, United States

Location

Related Publications (8)

• Kadam P, Bhalerao S. Sample size calculation. Int J Ayurveda Res. 2010 Jan;1(1):55-7. doi: 10.4103/0974-7788.59946. No abstract available.

  PMID: 20532100 BACKGROUND

• Abdelmalek MF, Humar A, Stickel F, Andreone P, Pascher A, Barroso E, Neff GW, Ranjan D, Toselli LT, Gane EJ, Scarola J, Alberts RG, Maller ES, Lo CM; Sirolimus Liver Conversion Trial Study Group. Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial. Am J Transplant. 2012 Mar;12(3):694-705. doi: 10.1111/j.1600-6143.2011.03919.x. Epub 2012 Jan 10.

  PMID: 22233522 RESULT

• Backman L, Nicar M, Levy M, Distant D, Eisenstein C, Renard T, Goldstein R, Husberg B, Gonwa TA, Klintmalm G. FK506 trough levels in whole blood and plasma in liver transplant recipients. Correlation with clinical events and side effects. Transplantation. 1994 Feb 27;57(4):519-25.

  PMID: 7509516 RESULT

• Kong Y, Wang D, Shang Y, Liang W, Ling X, Guo Z, He X. Calcineurin-inhibitor minimization in liver transplant patients with calcineurin-inhibitor-related renal dysfunction: a meta-analysis. PLoS One. 2011;6(9):e24387. doi: 10.1371/journal.pone.0024387. Epub 2011 Sep 9.

  PMID: 21931704 RESULT

• Langone A, Steinberg SM, Gedaly R, Chan LK, Shah T, Sethi KD, Nigro V, Morgan JC; STRATO Investigators. Switching STudy of Kidney TRansplant PAtients with Tremor to LCP-TacrO (STRATO): an open-label, multicenter, prospective phase 3b study. Clin Transplant. 2015 Sep;29(9):796-805. doi: 10.1111/ctr.12581. Epub 2015 Aug 6.

  PMID: 26113208 RESULT

• Yoo MC, Vanatta JM, Modanlou KA, Campos L, Nezakatgoo N, Nair S, Eason JD. Steroid-free Liver Transplantation Using Rabbit Antithymocyte Globulin Induction in 500 Consecutive Patients. Transplantation. 2015 Jun;99(6):1231-5. doi: 10.1097/TP.0000000000000477.

  PMID: 25539464 RESULT

• Garnock-Jones KP. Tacrolimus prolonged release (Envarsus(R)): a review of its use in kidney and liver transplant recipients. Drugs. 2015 Feb;75(3):309-20. doi: 10.1007/s40265-015-0349-2.

  PMID: 25613762 RESULT

• Niel OR, Berthoux F, Albano L, Dahan P, Aoudia R, Gugenheim J, Cassuto E. Long-term glomerular filtration rate in liver allograft recipients according to the type of calcineurin inhibitors. Transplant Proc. 2009 Oct;41(8):3329-32. doi: 10.1016/j.transproceed.2009.09.034.

  PMID: 19857743 RESULT

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• James Eason, MD

  The University of Tennessee Health Science Center, Department of Transplant

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will be a prospective, randomized, open label study comparing Envarsus XR with twice daily prograf.

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: February 4, 2019
• Study Start: April 1, 2019
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: January 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)