Early Use of Long-acting Tacrolimus in Lung Transplant Recipients

• Status: Not yet recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Collaborator: Veloxis Pharmaceuticals
• Treatments: Azathioprine; Mycophenolic Acid; Prednisone; Tacrolimus

Criteria

Inclusion Criteria:

• Status-post single or bilateral lung transplantation

• Participant is able to give informed consent for participation in the study.

• Male or female age 18 years or above.

• Actively receives care at VUMC and is adherent with medical therapies.

Exclusion Criteria:

• History of prior organ transplantation

• History of tacrolimus use prior to transplantation

• Intolerance of tacrolimus (that precludes use)

• Having DSA pre-transplant (Positive virtual crossmatch)

• Active infection with Hepatitis B or C

• Active infection with Human Immunodeficiency Virus (HIV)

• Baseline AST / ALT > three times upper limit normal

• Primary graft dysfunction grade 3 at 72 hours

• Acute kidney injury during index hospitalization that does not resolve to two times the pre-transplant baseline value.

• Contraindication to PO (per os) intake of medications

• Impaired GI absorption (defined as sublingual administration of IR-tacro)

• History of frequent headaches

• Seizure history

• Cannot provide consent (at least verbally)

• Pregnancy or breast-feeding

• Participation in another interventional clinical trial