Early Use of Long-acting Tacrolimus in Lung Transplant Recipients

Summary

Lung transplantation is a life-saving therapy for patients with advanced lung disease, however, necessitates the use of life-long immunosuppressive therapy for the prevention of acute and chronic rejection. The backbone of immunosuppression is the calcineurin-inhibitor class, with tacrolimus being the preferred drug due to its potency and improved side-effect profile. Nevertheless, tacrolimus is associated with several side effects including increased risk for infection and malignancy, tremors, headaches, seizures, hypertension, leukopenia and renal dysfunction. In fact, by 6 months post-transplant, 50% of patients will have a 50% decline in eGFR and by 5 years post-transplant \~10% of patients will have advanced renal disease that may require renal replacement therapy and/or kidney transplantation. Tacrolimus induces a nephropathy in two ways- acute calcineurin inhibitor nephrotoxicity (CIN) is mediated by afferent arteriolar vasoconstriction, whereas chronic CIN is due to interstitial nephritis and fibrosis. Immunosuppressive regimens that spare or dose-reduce calcineurin inhibitors have been shown to have a modest impact on preserving renal function, but are limited by timing. Although most studies support implementing renal preserving protocols early on, this is balanced by the potential for acute cellular rejection, antibody mediated rejection and anastomotic dehiscence.

Long-acting Tacrolimus (LCP-tacrolimus) may have the potential to bridge the balance of providing potent immunosuppression, while sparing renal function, due to the better systemic dose levels and improved concentration/dose ration achieved with it compared to IR-tacrolimus, evidenced in the renal transplant population. There is limited experience with LCP-tacrolimus in lung transplantation. Several case reports chronicling the late conversion from IR-tacrolimus to LCP-tacrolimus due to absorption issues or side-effect intolerance, have demonstrated safety and tolerability. The investigators seek to determine whether early use of LCP-tacrolimus in lung transplant recipients following the index hospitalization is acceptable, and propose a single-center prospective, randomized, controlled pilot study of early-use LCP-tacrolimus in lung transplant recipients to assess safety, tolerability and side-effects of LCP-tacrolimus.

Conditions

• Lung Transplant; Complications

Interventions

DRUG

Tacrolimus Extended Release Oral Tablet [Envarsus]

Immunosuppression regimen with Tacrolimus Extended Release as the backbone.

DRUG

Tacrolimus

Standard Immunosuppression regimen with Intermediate-Release Tacrolimus.

DRUG

Mycophenolate Mofetil Hydrochloride

Standard immunosuppression of the anti-proliferative class.

DRUG

Prednisone

Standard immunosuppression (corticosteroid class).

DRUG

Azathioprine

Standard immunosuppression of the anti-proliferative class.

Sponsors & Collaborators

• Veloxis Pharmaceuticals

  collaborator INDUSTRY

• Vanderbilt University Medical Center

  lead OTHER

Principal Investigators

• Anil J Trindade, MD · Vanderbilt University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-01

Primary Completion

2027-06-30

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States

Study Locations