Evaluate the Efficacy and Safety of the ADVAGRAF®

NCT04763096 | Completed Phase 4

• 1 other identifier: STABLE
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to evaluate the efficacy of 6-month treatment with Advagraf® converted from 12-month treatment with tacrolimus in stable liver transplant recipients. The secondary objective of this study is to evaluate severity of acute rejection confirmed by biopsy in 24 weeks, incidence of chronic rejection, patient and graft survival rates in 24 weeks, incidence of adverse events, blood pressure, tacrolimus trough level, drug compliance, and adherence.

Conditions

Evidence of Liver Transplantation

Keywords

ADVGRAF®, Liver transplantation, tacrolimus.

Outcome Measures

Primary Outcomes (1)

• Incidence of acute rejection confirmed by biopsy in 24 weeks after conversion

  * Incidence of acute rejection (%) = no. of subjects who had acute rejection at least once / no. of all the subjects in the relevant analysis set \* 100 * Only acute rejection confirmed by biopsy will be recognized. * In addition, concomitant immunosuppressants other than tacrolimus will be divided into sub-groups (by type and dosage/administration), and point estimation and calculation of 95% two-sided confidence interval will be conducted for incidence of acute rejection.

  within 24 weeks

Secondary Outcomes (7)

• Severity of acute rejection confirmed by biopsy in 24 weeks after conversion

  within 24 weeks

• Incidence of chronic rejection

  within 24 weeks

• Patient and graft survival rates in 24 weeks after conversion

  within 24 weeks

• Time from conversion to onset of acute rejection

  within 24 weeks

• Tacrolimus trough level at each visit

  within 24 weeks

Study Arms (1)

tacrolimus

EXPERIMENTAL

conversion to Advagraf

Drug: Advagraf

Interventions

Advagraf DRUG

Researchers must check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5\~10ng/ml of study treatment. Duration of treatment The investigational product will be administered for 24 weeks. (The lowest blood levels shall be adjusted at the discretion of the researchers, taking a blood sample is carried out in the morning before administrated of Investigational Product) Tacrolimus blood level is 3-10 ng/ml for 6 months prior to screening and during the maintenance therapy. ( ① -1day to enrollment : swich to the day before ADVAGRAF®, ② 0day to enrollment : the day swich to ADVAGRAF® ) Duration of treatment the investigational product will be administered for 24 weeks.

Also known as: tacrolimus

tacrolimus

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 19 and 80 years old
• Those who were transplantated liver at a minimum of 12 month of screening and after 12 month Treatment with a Tacrolimus stably.(Brain dead transplantation or biological transplant no values)
• tacrolimus blood everage level is 3-10 ng/ml for at least 6 months prior to screening.
• Female subjects of child bearing potential must have a negative urine or serum pregnancy test prior to enrollment and at the end of study and must agree to practice effective birth control during the study.
• Subjects are stable clinically in the opinion of the investigator.
• Subjects capable of understanding the purpose and risks of the study, having been fully informed and has given written informed consent to participate in the study

You may not qualify if:

• Subjects having previously received an organ transplant excluding liver transplant. Or Subjects receiving an auxiliary graft or in whom a bio-artificial liver(cell system) has been used.
• Acute rejection confirmed by histologic response or the patient had chronic rejection
• Subjects diagnosed new malignant tumor before the pre-screening within five years , with the exception of basalioma or squamous cell carcinoma or carcinoma in situ of the skin that has been treated successfully.
• Subjects allergic to tacrolimus or investigational product.
• Subjects are unstable clinically state in the opinion of the investigator.
• Subjects with any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator.
• Subjects participating or having participated in another clinical trial and/or those taking or having taken an investigational / non-registered drug in the past 28 days.
• Subjects taking forbidden concomitant medications or within 28 days prior to enroll.
• Subjects who are pregnant or breast-feeding mother.
• Subjects unlikely to comply with the visits scheduled in the protocol.
• Subjects with renal dysfunction on the investigator's point of view or serum creatinine \> 1.6mg/dL or GFR(MDRD)\<30mL/min in the baseline.
• Hepatic dysfunction: rising more than double the normal range of SGPT/ALT and/or SGOT/AST and/or bilirubin, hepatic cirrhosis

Sponsors & Collaborators

• Linical Korea: lead
• Asan Medical Center: collaborator

Study Sites (1)

Seoul Asan Medical Center

Seoul, 05505, South Korea

Location

Related Publications (10)

• Bunzel B, Laederach-Hofmann K. Solid organ transplantation: are there predictors for posttransplant noncompliance? A literature overview. Transplantation. 2000 Sep 15;70(5):711-6. doi: 10.1097/00007890-200009150-00001.

  PMID: 11003346 RESULT

• Laederach-Hofmann K, Bunzel B. Noncompliance in organ transplant recipients: a literature review. Gen Hosp Psychiatry. 2000 Nov-Dec;22(6):412-24. doi: 10.1016/s0163-8343(00)00098-0.

  PMID: 11072057 RESULT

• Schweizer RT, Rovelli M, Palmeri D, Vossler E, Hull D, Bartus S. Noncompliance in organ transplant recipients. Transplantation. 1990 Feb;49(2):374-7. doi: 10.1097/00007890-199002000-00029.

  PMID: 2305467 RESULT

• Jain AB, Kashyap R, Rakela J, Starzl TE, Fung JJ. Primary adult liver transplantation under tacrolimus: more than 90 months actual follow-up survival and adverse events. Liver Transpl Surg. 1999 Mar;5(2):144-50. doi: 10.1002/lt.500050209.

  PMID: 10071354 RESULT

• Dopazo C, Rodriguez R, Llado L, Calatayud D, Castells L, Ramos E, Molina V, Garcia R, Fabregat J, Charco R. Successful conversion from twice-daily to once-daily tacrolimus in liver transplantation: observational multicenter study. Clin Transplant. 2012 Jan-Feb;26(1):E32-7. doi: 10.1111/j.1399-0012.2011.01521.x. Epub 2011 Sep 30.

  PMID: 21958123 RESULT

• Trunecka P, Boillot O, Seehofer D, Pinna AD, Fischer L, Ericzon BG, Troisi RI, Baccarani U, Ortiz de Urbina J, Wall W; Tacrolimus Prolonged Release Liver Study Group. Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation. Am J Transplant. 2010 Oct;10(10):2313-23. doi: 10.1111/j.1600-6143.2010.03255.x. Epub 2010 Sep 14.

  PMID: 20840481 RESULT

• Comuzzi C, Lorenzin D, Rossetto A, Faraci MG, Nicolini D, Garelli P, Bresadola V, Toniutto P, Soardo G, Baroni GS, Adani GL, Risaliti A, Baccarani U. Safety of conversion from twice-daily tacrolimus (Prograf) to once-daily prolonged-release tacrolimus (Advagraf) in stable liver transplant recipients. Transplant Proc. 2010 May;42(4):1320-1. doi: 10.1016/j.transproceed.2010.03.106.

  PMID: 20534291 RESULT

• Merli M, Di Menna S, Giusto M, Giannelli V, Lucidi C, Loria I, Ginanni Corradini S, Mennini G, Rossi M. Conversion from twice-daily to once-daily tacrolimus administration in liver transplant patient. Transplant Proc. 2010 May;42(4):1322-4. doi: 10.1016/j.transproceed.2010.04.012.

  PMID: 20534292 RESULT

• Marin-Gomez LM, Gomez-Bravo MA, Alamo-Martinez JA, Barrera-Pulido L, Bernal Bellido C, Suarez Artacho G, Pascasio JM. Evaluation of clinical safety of conversion to Advagraf therapy in liver transplant recipients: observational study. Transplant Proc. 2009 Jul-Aug;41(6):2184-6. doi: 10.1016/j.transproceed.2009.06.085.

  PMID: 19715867 RESULT

• Kim SH, Lee SD, Kim YK, Park SJ. Conversion of twice-daily to once-daily tacrolimus is safe in stable adult living donor liver transplant recipients. Hepatobiliary Pancreat Dis Int. 2015 Aug;14(4):374-9. doi: 10.1016/s1499-3872(15)60378-2.

  PMID: 26256081 RESULT

Related Links

• test link(2000 Sep 15;70(5):711-6.)
• test link(2000 Nov-Dec;22(6):412-24.)
• test link(1990 Feb;49(2):374-7.)
• test link(1999 Mar;5(2):144-50.)
• test link(2012 Jan-Feb;26(1):E32-7. doi: 10.1111/j.1399-0012.2011.01521.x. Epub 2011 Sep 30.)
• test link(2010 Oct;10(10):2313-23. doi: 10.1111/j.1600-6143.2010.03255.x. Epub 2010 Sep 14.)
• test link( 2010 May;42(4):1320-1. doi: 10.1016/j.transproceed.2010.03.106.)
• test link(2010 May;42(4):1322-4. doi: 10.1016/j.transproceed.2010.04.012.)
• test link(2009 Jul-Aug;41(6):2184-6. doi: 10.1016/j.transproceed.2009.06.085.)
• test link(2015 Aug;14(4):374-9.)

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Ki Won Song, doctral

  Asan Medical Center, Hepatobiliary, Liver Transplantion Surgery center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: February 21, 2021
• Study Start: November 1, 2016
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share

Locations

KR (1)