Early Use of Long-acting Tacrolimus in Lung Transplant Recipients

Part of paid clinical trials in Nashville, Tennessee.

Sponsor
Vanderbilt University Medical Center
Study ID
NCT04469842
Phase
EARLY_PHASE1
Status
Recruiting
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Conditions

  • Lung Transplant; Complications

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tacrolimus Extended Release Oral Tablet [Envarsus] — DRUG
    Immunosuppression regimen with Tacrolimus Extended Release as the backbone.
  • Tacrolimus — DRUG
    Standard Immunosuppression regimen with Intermediate-Release Tacrolimus.
  • Mycophenolate Mofetil Hydrochloride — DRUG
    Standard immunosuppression of the anti-proliferative class.
  • Prednisone — DRUG
    Standard immunosuppression (corticosteroid class).
  • Azathioprine — DRUG
    Standard immunosuppression of the anti-proliferative class.

Study Details

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.

Key Dates

Start date
Dec 1, 2023
Status verified
May 2026
Primary completion
Jun 30, 2027
Completion
Dec 31, 2027

Study Design

Enrollment
48 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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.

Primary Outcome Measure

Safety and Tolerability [ Time Frame: 6 months ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Vanderbilt University Medical CenterNashvilleTennessee37232
Anil J. Trindade, MD
[email protected]
615-875-1380
Anil J Trindade, MD (PRINCIPAL_INVESTIGATOR)
Haley Hoy, PhD, NP (SUB_INVESTIGATOR)
Amit Parulekar, MD (SUB_INVESTIGATOR)
Ivan Robbins, MD (SUB_INVESTIGATOR)
Ciara Shaver, MD, PhD (SUB_INVESTIGATOR)
Stephanie Norfolk, MD (SUB_INVESTIGATOR)
Katie McPherson, MD (SUB_INVESTIGATOR)

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Vanderbilt University Medical Center· Nashville, TN

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