A Prospective, Randomized, Controlled Pilot Study of Early-Use Long Acting Tacrolimus (Envarsus XR) in Lung Transplant Recipients

Who is this study for? Patients who are lung transplant recipients
What treatments are being studied? Tacrolimus
Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Early Phase 1
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

Locations
United States
Tennessee
Vanderbilt University Medical Center
RECRUITING
Nashville
Contact Information
Primary
Anil J Trindade, MD
anil.trindade@vumc.org
615-875-1380
Backup
Haley Hoy, PhD, NP
haley.hoy@vumc.org
615-202-8576
Time Frame
Start Date: 2023-12-01
Estimated Completion Date: 2026-12-31
Participants
Target number of participants: 48
Treatments
Experimental: Immunosuppression with Extended-Release Tacrolimus
LCP-tacrolimus administered daily to target a goal trough level of 10-14 ng/mL x 7 months (with Mycophenolate mofetil and prednisone).~Additional standard immunosuppression with either mycophenolate mofetil (500-1500mg twice daily) OR Azathioprine (up to 2mg/kg daily) AND Prednisone (5-10mg daily) will be administered.
Active_comparator: Immunosuppression with Intermediate Release Tacrolimus
IR-tacrolimus administered twice daily to target a goal trough level of 10-14 ng/mL x 7 months (with Mycophenolate mofetil and prednisone). This is currently the standard of care at Vanderbilt University Medical Center and most other lung transplant centers (ISHLT Registry 2019).~Additional standard immunosuppression with either mycophenolate mofetil (500-1500mg twice daily) OR Azathioprine (up to 2mg/kg daily) AND Prednisone (5-10mg daily) will be administered.
Sponsors
Leads: Vanderbilt University Medical Center
Collaborators: Veloxis Pharmaceuticals

This content was sourced from clinicaltrials.gov