Trial Comparing Immediate Versus Extended Release Tacrolimus; Reducing Calcineurin Inhibitor Related Toxicity in Lung Transplantation Patients

NCT05001074 | Unknown Phase 3

• 1 other identifier: 202000134
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief Summary

Lung transplantation is a life-saving option in patients with end-stage lung disease. The introduction of calcineurin inhibitors has significantly improved long-term outcome in lung transplantation. The most frequently used calcineurin inhibitor as maintenance therapy is immediate release tacrolimus, dosed twice daily, which has shown to reduce both acute and chronic rejection. However, a drawback to the administration of tacrolimus is its toxicity. Especially progressive renal toxicity, new onset diabetes and hypertension contribute to the high cardiovascular burdon in this patient group. Since a few years an once daily extended release tacrolimus has been introduced in solid organ transplantation. The advantage of extended release tacrolimus is its prolonged release and higher bioavailability than other tacrolimus formulations. This result in lower peaks, more stable serum levels over 24 hours, and less fluctuation of blood concentrations. Long-term toxicity outcome of extended release tacrolimus after lung transplantation has not been studied so far. Therefore the potential benefit of exteded release tacrolimus in de novo and stable post-lung transplant recipients should be investigated.

Conditions

Lung Transplant; Complications

Keywords

lung transplantation; chronic kidney disease; cardiovascular disease; extended release tacrolimus; LCP tacrolimus; immediate release tacrolimus

Outcome Measures

Primary Outcomes (1)

• renal function: absolute change in eGFR

  absolute change in eGFR absolute change in eGFR change in eGFR at 2 years

  2 years

Secondary Outcomes (15)

• graft function

  2 years

• renal function: 40% eGFR reduction

  2 years

• renal function: 50% eGFR reduction

  2 years

• renal function:end stage kidney disease

  2 years

• hypertension

  2 years

Study Arms (4)

de novo cohort, extended release tacrolimus

EXPERIMENTAL

de novo cohort, extended release tacrolimus

Drug: Extended release tacrolimus

de novo cohort, immediate release tacrolimus

ACTIVE COMPARATOR

de novo cohort, immediate release tacrolimus

Drug: Immediate release tacrolimus

conversion cohort, extended release tacrolimus

EXPERIMENTAL

conversion cohort, extended release tacrolimus

Drug: Extended release tacrolimus

conversion cohort, immediate release tacrolimus

ACTIVE COMPARATOR

conversion cohort, immediate release tacrolimus

Drug: Immediate release tacrolimus

Interventions

Extended release tacrolimus DRUG

de novo cohort: participants are randomised for extended release tacrolimus or immediate release tacrolimus direct post-lung transplantation Conversion cohort: participants are randomised for extended release tacrolimus or immediate release tacrolimus when \>1 year post-lungtransplantation and with stable graft function

Also known as: LCP tacrolimus

conversion cohort, extended release tacrolimus; de novo cohort, extended release tacrolimus

Immediate release tacrolimus DRUG

de novo cohort: participants are randomised for extended release tacrolimus or immediate release tacrolimus direct post-lung transplantation Conversion cohort: participants are randomised for extended release tacrolimus or immediate release tacrolimus when \>1 year post-lungtransplantation and with stable graft function

conversion cohort, immediate release tacrolimus; de novo cohort, immediate release tacrolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Single or bilateral lung transplantation
• On twice daily tacrolimus with stable trough levels in target range
• Participant in the TransplantLines biobank study in the UMCG
• Additional criteria for Conversion cohort:
• At least one year after lung transplantation with a stable clinical course and lung function
• eGFR \>30ml/min\*1.73m2 calculated with the CKD-EPI formula

You may not qualify if:

• Administration of mTOR inhibitors; everolimus, sirolimus
• Quadruple immunosuppression
• Renal transplantation
• The subject has any disease or condition that might interfere with completion of this study or reaching the primary endpoint (e.g., life expectancy of \<3 years, renal replacement therapy at start study)

Sponsors & Collaborators

• Heleen Grootjans: lead
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (1)

University medical center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Related Publications (4)

• Sintes H, Saez-Gimenez B, Berastegui C, Lopez-Meseguer M, Monforte V, Bravo C, Vima J, Gomez-Olles S, Roman A. Pharmacokinetic Study of Conversion Between 2 Formulations of Once-daily Extended-release Tacrolimus in Stable Lung Transplant Patients. Transplantation. 2018 Oct;102(10):e439-e446. doi: 10.1097/TP.0000000000002348.

  PMID: 29965950 RESULT

• Mendez A, Berastegui C, Lopez-Meseguer M, Monforte V, Bravo C, Blanco A, Camos S, Pou L, Roman A. Pharmacokinetic study of conversion from tacrolimus twice-daily to tacrolimus once-daily in stable lung transplantation. Transplantation. 2014 Feb 15;97(3):358-62. doi: 10.1097/01.TP.0000435699.69266.66.

  PMID: 24492423 RESULT

• TruneCka P, Klempnauer J, Bechstein WO, Pirenne J, Friman S, Zhao A, Isoniemi H, Rostaing L, Settmacher U, Monch C, Brown M, Undre N, Tisone G; DIAMONDdagger study group. Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study. Am J Transplant. 2015 Jul;15(7):1843-54. doi: 10.1111/ajt.13182. Epub 2015 Feb 23.

  PMID: 25707487 RESULT

• Sanchez Fructuoso A, Ruiz JC, Franco A, Diekmann F, Redondo D, Calvino J, Serra N, Aladren MJ, Cigarran S, Manonelles A, Ramos A, Gomez G, Gonzalez Posada JM, Andres A, Beneyto I, Muniz AL, Perello M, Lauzurica R. Effectiveness and safety of the conversion to MeltDose(R) extended-release tacrolimus from other formulations of tacrolimus in stable kidney transplant patients: A retrospective study. Clin Transplant. 2020 Jan;34(1):e13767. doi: 10.1111/ctr.13767. Epub 2019 Dec 31.

  PMID: 31815310 RESULT

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tji Gan

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heleen Grootjans

CONTACT

0031503616161; h.grootjans@umcg.nl

Tji Gan

CONTACT

0031503616161; c.t.gan@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Drs. Heleen Grootjans, internist-nephrologist

Model Details: De novo cohort, 2 arms: de novo lung transplant recipients. Conversion cohort, 2 arms: stable lung transplant recipients

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: August 11, 2021
• Study Start: July 28, 2020
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)