Comparing two formulations of tacrolimus in kidney transplant recipients

Multicentre, Open-label, Randomised, Two-arm, Parallel-group, Superiority Trial to Assess Bioavailability and Practicability of Two Once-daily Tacrolimus Formulations, Envarsus® Compared With Advagraf™, Administered in Kidney Transplant Recipients

This study is testing which of two different once-daily versions of a kidney transplant medication, Envarsus® or Advagraf™, works better and is easier to manage for patients after their transplant.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Regensburg (Academic / other)
• Locations: 9 sites (Aachen and 8 other locations)
• Trial ID: NCT06268769 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to compare the bioavailability and practicability of two once-daily formulations of tacrolimus, Envarsus® and Advagraf™, in patients undergoing kidney transplantation. Participants will be randomized to receive either formulation within 7 days prior to surgery, and their tacrolimus blood levels will be monitored to assess the concentration/dose ratio at 12 weeks post-transplant. The study will also evaluate the ease of handling these medications and their relationship to long-term clinical outcomes, including adverse reactions over a three-year period.

Who should consider this trial

Good fit: Ideal candidates for this study are adult patients aged 18 and older who require a first or second kidney transplant and are compatible with their donor's ABO blood type.

Not a fit: Patients who have undergone multi-organ transplantation or have a history of solid organ transplantation other than a first kidney allograft may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved immunosuppressive treatment options for kidney transplant recipients, enhancing graft survival and patient outcomes.

How similar studies have performed: Previous studies have shown promising results with similar approaches in evaluating tacrolimus formulations, suggesting potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

1. Signed and dated written informed consent
2. Adult (≥18 years old) male or female
3. Renal insufficiency necessitating kidney transplantation and approved to receive a first or second kidney allograft from a living or deceased organ donor
4. ABO blood type compatible with the donor kidney
5. Able to swallow an oral formulation of tacrolimus in tablet or capsule form

Exclusion Criteria:

1. Multi-organ transplantation
2. Any previous solid organ transplantation (other than a first kidney allograft)
3. For recipients of a second kidney transplant: loss of first kidney transplant within 2 years after transplantation owing to immunological reasons or recurrence of the underlying renal disease
4. Patient and/or donor is positive for HCV, HBV or HIV
5. History of any malignancy that could not be curatively treated
6. Ongoing abuse of drugs or alcohol
7. Signs of advanced liver disease or any signs of liver decompensation
8. Ongoing uncontrolled systemic infection
9. Severe diarrhoea, vomiting, active peptic ulcer, previous bariatric surgery, or any other gastrointestinal disorder that may affect absorption of tacrolimus
10. Planned or foreseeable use of cyclosporine, belatacept or any tacrolimus preparation other than Envarsus® or Advagraf™
11. Known contraindication or hypersensitivity to tacrolimus, and/or to any of the excipients listed in section 6.1 of the Summary of Product Characteristics (SmPC) of both Envarsus® and Advagraf™, and/or to any other macrolides
12. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
13. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless using a highly-effective method of contraception
14. Participation in another interventional clinical trial in the time period starting from 4 weeks prior to randomisation and throughout the entire trial period
15. Any condition or factor which, in the judgement of the investigator, would place the subject at undue risk, invalidate communication with the investigator or study team, or hamper compliance with the trial protocol or follow-up schedule
16. Inability to freely give informed consent (e.g. individuals under legal guardianship)

Where this trial is running

Aachen and 8 other locations

• University Hospital Aachen, Department of General, Visceral and Transplant Surgery — Aachen, Germany (Not_yet_recruiting)
• Charité Universitätsmedizin, Department of Nephrology and Medical Intensive Care — Berlin, Germany (Not_yet_recruiting)
• University Hospital Dresden, Division of Nephrology — Dresden, Germany (Recruiting)
• University Medical Center Hamburg-Eppendorf, Internal Medicine III (Nephrology, Rheumatology, Endocrinology) — Hamburg, Germany (Recruiting)
• Hannover Medical School, Department of General, Visceral and Transplant Surgery — Hanover, Germany (Recruiting)
• University Hospital Jena, Internal Medicine III, Nephrology — Jena, Germany (Recruiting)
• University Medical Center of the Johannes Gutenberg University Mainz, Medical Clinic I. (Nephrology) — Mainz, Germany (Not_yet_recruiting)
• University Hospital Münster, Medical Clinic D — Münster, Germany (Not_yet_recruiting)
• University Hospital Regensburg, Department of Nephrology — Regensburg, Germany (Recruiting)

Study contacts

• Principal investigator: Bernhard Banas, MD — University Hospital Regensburg
• Study coordinator: Edward K. Geissler, PhD

Conditions Immunosuppression; Kidney transplantation; Tacrolimus; Concentration/dose ratio