Extended Release Tacrolimus for Lung Transplant Complications

Overseen By Haley Hoy, PhD, NP

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must be taking: Immunosuppressants

Must not be taking: Antivirals

Disqualifiers: Prior organ transplant, Hepatitis B/C, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 7 months

48 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Anil Trindade, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for adults over 18 who have had a lung transplant, can consent to the study, and are treated at VUMC with good adherence to medical therapies. It's not for those with certain infections (Hepatitis B/C, HIV), high liver enzymes, unresolved kidney injury post-transplant, issues taking oral meds, pregnant or breastfeeding women, severe graft dysfunction post-transplantation, GI absorption problems, prior organ transplants or tacrolimus intolerance.

Inclusion Criteria

I have had a lung transplant.

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

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

Exclusion Criteria

I have a history of seizures.

You are currently enrolled in another study where you are receiving a treatment.

I often have headaches.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either IR-tacrolimus or LCP-tacrolimus for immunosuppression post-lung transplant

7 months

Regular visits for monitoring trough levels and side effects

Follow-up

Participants are monitored for safety, tolerability, and effectiveness of the treatment

2 months

Visits for eGFR assessment and quality of life evaluations

Extension

Optional continuation of monitoring for long-term outcomes

Long-term

Treatment Details

Interventions

• Azathioprine
• Mycophenolate Mofetil Hydrochloride
• Prednisone
• Tacrolimus
• Tacrolimus Extended Release Oral Tablet [Envarsus]

Trial Overview The study tests if early use of Long-acting Tacrolimus (LCP-tacrolimus) after lung transplantation is safe and tolerable compared to immediate-release tacrolimus. The goal is to see if LCP-tacrolimus better preserves kidney function while still preventing rejection of the new lungs.

Participant Groups

Group I: Immunosuppression with Extended-Release Tacrolimus Experimental Treatment 4 Interventions

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.

Group II: Immunosuppression with Intermediate Release Tacrolimus Active Control 4 Interventions

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.

Azathioprine is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Imuran for:

• Prevention of rejection in organ transplantation
• Treatment of autoimmune diseases such as rheumatoid arthritis

Approved in United States as Imuran for:

• Prevention of rejection in organ transplantation
• Treatment of rheumatoid arthritis

Approved in Canada as Imuran for:

• Prevention of rejection in organ transplantation
• Treatment of rheumatoid arthritis

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Veloxis Pharmaceuticals

Industry Sponsor

Trials

43

Recruited

3,200+