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Chronic Kidney DiseasesPhase 4NCT04917718

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

A Phase 4 study testing Conversion from IR Tacrolimus to XR Tacrolimus in people with Chronic Kidney Diseases and Heart Transplant, run by Loyola University at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Chronic Kidney Diseases, Heart Transplant
What is being tested?
Conversion from IR Tacrolimus to XR Tacrolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
16 Aug 2021to 31 Dec 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Stable, heart-only transplant recipient within 10 years of transplantation
  • 18 -80 years old
  • Currently taking IR Tacrolimus
  • Baseline eGFR> 30mL/min/1.73m2

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Sanjeev Akkina, MD contact

708-327-4897

sanjeev.akkina@lumc.edu

United States1 site, 1 recruiting

  • Loyola University Medical Center

    Maywood, Illinois, 60153

    Recruiting

Other trials in United States

About this study

Official title: Assessment of Renal Tubular Injury and Transplant Outcomes in Cardiac Recipients Converting From Immediate Release Tacrolimus to Extended Release Tacrolimus.

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.

Read the detailed description

The primary outcome is change in urinary NGAL expression with conversion from IR tacrolimus to tacrolimus XR. In aim 1, changes in urinary biomarkers of tubular injury at 4 weeks after conversion to tacrolimus XR with stable trough levels will be assessed. These changes will be assessed by CYP3A5 expressor category that will be determined by genotyping of a single gene for variants. The changes in GFR using the creatinine-cystatin C CKD-EPI equation will be assessed. In aim 2, the rate of rejection as defined as treated rejection within the last 30 days for any grade > 1R or AMR or acute graft dysfunction (LV ejection fraction drop > 10%) will be looked. The cardiac allograft vasculopathy based on coronary angiography +/- IVUS and right heart catheterization hemodynamics at baseline and 1 year post conversion will also be evaluated. In addition to changes in cardiac function, the changes in blood pressure, serum glucose, and cholesterol in the first year after conversion will be assessed.

Being tested
Conversion from IR Tacrolimus to XR Tacrolimus
Keywords
Immediate Release Tacrolimus, Extended Release Tacrolimus, IR Tacrolimus, XR Tacrolimus, Renal Tubular Injury, Heart Transplant Recipient, Chronic Kidney Disease
Medical subject headings
Renal Insufficiency, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Conversion from IR Tacrolimus to XR TacrolimusDrug

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

Study groups in NCT04917718
Study groupRoleWhat they receive
Extended Release TacrolimusExperimentalAll participants who consent to the study will be in this group.
Receives: Drug: Conversion from IR Tacrolimus to XR Tacrolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Urinary neutrophil gelatinase-associated lipocalin (NGAL)

    Change in Urinary NGAL level (ng/mL)

    Measured: 4 weeks

Secondary outcomes (8)

  1. Estimated Glomerular Filtration Rate (eGFR)

    Change in eGRF level by the Creatinine-Cystatin C CKD-EPI equation (mL/min/1.73m2)

    Measured: 4 weeks

  2. Microalbuminuria

    Change in Urine albumin-creatinine ratio

    Measured: 4 weeks

  3. CYP3A5 expressor category

    CYP3A5 genotyping to determine expressor category

    Measured: Baseline

  4. Heart transplant rejection

    The rate of rejection as defined as treated rejection within the last 30 days for any grade>1R, AMR, or acute graft dysfunction (LVEF drop greater than 10%)

    Measured: 1 year

  5. Cardiac allograft vasculopathy

    The rate of cardiac allograft vasculopathy based on coronary angiography with or without IVUS and right heart catheterization hemodynamics

    Measured: 1 year

  6. Blood pressure

    Change in blood pressure (mmHg)

    Measured: 1 year

  7. Serum glucose

    Change in serum glucose levels (mg/dL)

    Measured: 1 year

  8. LDL Cholesterol

    Change in LDL cholesterol level (mg/dL)

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2021
  2. Study start16 Aug 2021
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04917718
Sponsor's protocol ID
212781
Status last verified
Apr 2022
First submitted
2 Jun 2021
Last updated
13 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 12954741

  • 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.

    PubMed 19218475

  • 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.

    PubMed 11265958

  • 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.

    PubMed 6382005

  • 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.

    PubMed 17318073

  • 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.

    PubMed 29162334

  • 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.

    PubMed 23279614

  • 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.

    PubMed 30576367

  • 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.

    PubMed 20458318

  • 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.

    PubMed 25329716

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Conversion from IR Tacrolimus to XR Tacrolimus in people with Chronic Kidney Diseases and Heart Transplant, run by Loyola University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 13 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Sanjeev Akkina, MD (708-327-4897, sanjeev.akkina@lumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Urinary neutrophil gelatinase-associated lipocalin (NGAL) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04917718, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2022.

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