drugset / Trial / NCT04469842

Early Use of Long-acting Tacrolimus in Lung Transplant Recipients

Phase 0 Recruiting 48 enrolled Vanderbilt University Medical Center Veloxis Pharmaceuticals · collab

RandomizedParallel-groupOpen-labelTreatment

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.

Timeline

Start: 2023-12-01
Primary completion: 2027-06-30
Completion: 2027-12-31

Publications

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Tacrolimus	Small molecule	—	Oral
Background	Azathioprine	Small molecule	2 mg/kg	—
Background	Mycophenolate Mofetil	Small molecule	500 mg	—
Background	Mycophenolate Mofetil	Small molecule	1500 mg	—
Background	Prednisone	Other / unclassified	5 mg	—
Background	Prednisone	Other / unclassified	10 mg	—

Early Use of Long-acting Tacrolimus in Lung Transplant Recipients

Summary

Timeline

Publications

Drugs

Indications