Renal Tubular Injury and Transplant Outcomes in Cardiac Recipients Converting From IR Tacrolimus to XR Tacrolimus

NCT04917718 | Unknown Phase 4 FDA Drug

• 1 other identifier: 212781
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Immediate release (IR) tacrolimus peaks in the first two hours after administration. These peak levels are influenced by CYP3A5 expression with expressors requiring higher total daily doses with higher peak levels compared to non-expressors. Tacrolimus XR (Envarsus) is a once daily formulation with delayed absorption and lower peak levels while maintaining similar trough levels as seen with IR tacrolimus. A randomized trial of conversion from IR tacrolimus to tacrolimus XR in kidney transplant recipients have shown similar efficacy and adverse events between the two groups but no improvement in estimated GFR. However, urinary biomarkers of acute kidney injury associated with changes in tacrolimus dosing may be more sensitive then serum creatinine. The objective of this study is to assess renal tubular injury in heart transplant recipients who are converted from immediate release to tacrolimus XR. The hypothesis is that the delayed absorption and lower peak levels of tacrolimus XR will lead to less tubular injury and improved renal function without increased risk to the heart allograft.

Conditions

Chronic Kidney Diseases; Heart Transplant

Keywords

Immediate Release Tacrolimus; Extended Release Tacrolimus; IR Tacrolimus; XR Tacrolimus; Renal Tubular Injury; Heart Transplant Recipient; Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Urinary neutrophil gelatinase-associated lipocalin (NGAL)

  Change in Urinary NGAL level (ng/mL)

  4 weeks

Secondary Outcomes (8)

• Estimated Glomerular Filtration Rate (eGFR)

  4 weeks

• Microalbuminuria

  4 weeks

• CYP3A5 expressor category

  Baseline

• Heart transplant rejection

  1 year

• Cardiac allograft vasculopathy

  1 year

Study Arms (1)

Extended Release Tacrolimus

EXPERIMENTAL

All participants who consent to the study will be in this group.

Drug: Conversion from IR Tacrolimus to XR Tacrolimus

Interventions

Conversion from IR Tacrolimus to XR Tacrolimus DRUG

All participants will be consented to the study on IR Tacrolimus. After their baseline visit, they will be converted to XR Tacrolimus

Extended Release Tacrolimus

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stable, heart-only transplant recipient within 10 years of transplantation
• years old
• Currently taking IR Tacrolimus
• Baseline eGFR\> 30mL/min/1.73m2

You may not qualify if:

• Multiple organ transplant recipients
• Less than 18 years old
• Greater than 80 years old
• Heart-only transplants recipients with active malignancy, rejection, or greater than 10 years from transplantation

Sponsors & Collaborators

• Loyola University: lead
• Veloxis Pharmaceuticals: collaborator

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

RECRUITING

Related Publications (10)

• Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, Arndorfer J, Christensen L, Merion RM. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003 Sep 4;349(10):931-40. doi: 10.1056/NEJMoa021744.

  PMID: 12954741 BACKGROUND

• Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol. 2009 Feb;4(2):481-508. doi: 10.2215/CJN.04800908.

  PMID: 19218475 BACKGROUND

• Camara NO, Matos AC, Rodrigues DA, Pereira AB, Pacheco-Silva A. Early detection of heart transplant patients with increased risk of ciclosporin nephrotoxicity. Lancet. 2001 Mar 17;357(9259):856-7. doi: 10.1016/S0140-6736(00)04207-0.

  PMID: 11265958 BACKGROUND

• Myers BD, Ross J, Newton L, Luetscher J, Perlroth M. Cyclosporine-associated chronic nephropathy. N Engl J Med. 1984 Sep 13;311(11):699-705. doi: 10.1056/NEJM198409133111103.

  PMID: 6382005 BACKGROUND

• Cosio FG, Amer H, Grande JP, Larson TS, Stegall MD, Griffin MD. Comparison of low versus high tacrolimus levels in kidney transplantation: assessment of efficacy by protocol biopsies. Transplantation. 2007 Feb 27;83(4):411-6. doi: 10.1097/01.tp.0000251807.72246.7d.

  PMID: 17318073 BACKGROUND

• Trofe-Clark J, Brennan DC, West-Thielke P, Milone MC, Lim MA, Neubauer R, Nigro V, Bloom RD. Results of ASERTAA, a Randomized Prospective Crossover Pharmacogenetic Study of Immediate-Release Versus Extended-Release Tacrolimus in African American Kidney Transplant Recipients. Am J Kidney Dis. 2018 Mar;71(3):315-326. doi: 10.1053/j.ajkd.2017.07.018. Epub 2017 Nov 20.

  PMID: 29162334 BACKGROUND

• Bunnapradist S, Ciechanowski K, West-Thielke P, Mulgaonkar S, Rostaing L, Vasudev B, Budde K; MELT investigators. Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial. Am J Transplant. 2013 Mar;13(3):760-9. doi: 10.1111/ajt.12035. Epub 2012 Dec 21.

  PMID: 23279614 BACKGROUND

• Chancharoenthana W, Leelahavanichkul A, Wattanatorn S, Avihingsanon Y, Praditpornsilpa K, Eiam-Ong S, Townamchai N. Alteration of urinary neutrophil gelatinase-associated lipocalin as a predictor of tacrolimus-induced chronic renal allograft fibrosis in tacrolimus dose adjustments following kidney transplantation. PLoS One. 2018 Dec 21;13(12):e0209708. doi: 10.1371/journal.pone.0209708. eCollection 2018.

  PMID: 30576367 BACKGROUND

• Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S, Muniappa N, Thudium D, Gerhold D, Holder DJ, Bobadilla NA, Marrer E, Perentes E, Cordier A, Vonderscher J, Maurer G, Goering PL, Sistare FD, Bonventre JV. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol. 2010 May;28(5):478-85. doi: 10.1038/nbt.1623.

  PMID: 20458318 BACKGROUND

• Tsuchimoto A, Shinke H, Uesugi M, Kikuchi M, Hashimoto E, Sato T, Ogura Y, Hata K, Fujimoto Y, Kaido T, Kishimoto J, Yanagita M, Matsubara K, Uemoto S, Masuda S. Urinary neutrophil gelatinase-associated lipocalin: a useful biomarker for tacrolimus-induced acute kidney injury in liver transplant patients. PLoS One. 2014 Oct 20;9(10):e110527. doi: 10.1371/journal.pone.0110527. eCollection 2014.

  PMID: 25329716 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sanjeev Akkina, MD

  Loyola University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sanjeev Akkina, MD

CONTACT

708-327-4897; sanjeev.akkina@lumc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Associate Professor of Medicine

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 8, 2021
• Study Start: August 16, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 13, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)