Risk Factors of Chinese Kidney Transplant Recipients DSA Based on MPA Immunosuppressive Regimen

NCT04444843 | Unknown Phase 4

• 1 other identifier: ML40754
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

THE INCIDENCE AND INFLUENTIAL FACTORS OF DSA IN CHINESE RENAL TRANSPLANT RECIPIENTS WITH MPA-BASED IMMUNOSUPPRESSIVE REGIMEN： A MULTI-CENTER CLINICAL STUDY (TIAIFOD STUDY) Study procedure Investigators at participating centers will identify patients fulfilling inclusion criteria and do not violate any exclusion criteria. Informed consent will be obtained upon entry into the study according to national regulations. Patients will be enrolled into the study and clinical data of patient history will be collected. Clinical data will be collected prospectively up to a total period of 12 months.

Conditions

Kidney Transplant Recipients

Keywords

kidney transplant recipients; Mycophenolate Mofetil Capsules; Acute Rejection; Cyclosporine; Delayed graft function; Tacrolimus; Mycophenolic Acid Area under the Curve

Outcome Measures

Primary Outcomes (1)

• the incidence of Donor specific antibody(DSA) formation during 12-months post-transplantation

  the incidence of DSA formation during 12-months post-transplantation

  12-months

Secondary Outcomes (7)

• the incidence of DSA formation during 6-months post-transplantation

  6 months

• the influential factors of DSA formation

  12 months

• the association between DSA and MPA AUC

  12 months

• the calculation formula for MPA-AUC with ISS using multiple regression analysis

  12 months

• the proportion of patients experiencing Acute Rejection(AR), Biopsy proven acute rejection(BPAR), Antibody mediated rejection(ABMR) and the association with Donor specific antibody(DSA)

  12 months

Study Arms (1)

Mycophenolate Mofetil Capsules

OTHER

The dosage of mycophenolate mofetil (CellCept) will be decided by the investigator and should be adjusted according to clinical response or therapeutic drug monitoring. It is not allowed to switch to other MPAs. When MMF is discontinued but is not switched to other MPA, the patients will be followed until the end of study.

Drug: Mycophenolate Mofetil Capsules

Interventions

Mycophenolate Mofetil Capsules DRUG

Patients who received MMF+TAC+ Corticosteroids immunosuppressive regimen as first choice post transplantation

Also known as: Other MPAs

Mycophenolate Mofetil Capsules

Eligibility Criteria

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

You may qualify if:

• Male or female kidney transplant recipients from 18 to 65 years of age (including 18 \& 65 years old patients)
• Single organ and first kidney transplant recipients from donation after citizen's death
• Patients who received MMF+TAC+ Corticosteroids immunosuppressive regimen as first choice post transplantation
• Pre-transplant PRA is negative (0%)
• One serum pregnancy test with a sensitivity of at least 25mlU/Ml for patients of childbearing potential before enrolled. A second test should be performed 8-10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. Patients should be instructed to consult their physician immediately should pregnancy occur. For patients to be included in the study, negative result must be obtained. And highly effective contraception for women of childbearing potential. Contraception must be taken before beginning study drug therapy, during therapy and for 6 weeks after the last dose of study medication

You may not qualify if:

• Patients who do not receive MMF
• Patients who are re-transplantation or multiple organ transplantation recipients
• Female patients who are pregnant or lactating
• Patients who have any form of substance abuse, psychological illness or any other condition, which, in the opinion of the investigator, may interfere with the patient's ability to understand the requirements of the study.
• Patients who would have received another investigational drug within 30 days preceding the enrollment, received prohibited immunosuppressant medications prior to transplant
• Patients who are using AZA, MTX, CTX or will use these drugs post-transplantation
• Known contraindications to TAC , corticosteroids, MMF
• Patients who have active peptic ulcer
• Patients who have severe cardiac or lung disease
• Patient who have active hepatica disease
• Patients who have a history of cancer, except successfully treated localized nonmelanocytic skin cancer
• Patients who would not be available for routine study visits or follow-up, or not being followed by an accredited laboratory.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead

Study Sites (1)

First Affiliated Hospital Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

RECRUITING

Related Publications (30)

• Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999 Dec 2;341(23):1725-30. doi: 10.1056/NEJM199912023412303.

  PMID: 10580071 RESULT

• Huang J, Millis JM, Mao Y, Millis MA, Sang X, Zhong S. Voluntary organ donation system adapted to Chinese cultural values and social reality. Liver Transpl. 2015 Apr;21(4):419-22. doi: 10.1002/lt.24069. Epub 2015 Feb 13.

  PMID: 25545626 RESULT

• Miettinen J, Perasaari J, Lauronen J, Qvist E, Valta H, Pakarinen M, Merenmies J, Jalanko H. Donor-specific HLA antibodies and graft function in children after renal transplantation. Pediatr Nephrol. 2012 Jun;27(6):1011-9. doi: 10.1007/s00467-012-2101-4. Epub 2011 Oct 13.

  PMID: 21993970 RESULT

• Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004 Mar;4(3):378-83. doi: 10.1111/j.1600-6143.2004.00332.x.

  PMID: 14961990 RESULT

• Ginevri F, Nocera A, Comoli P, Innocente A, Cioni M, Parodi A, Fontana I, Magnasco A, Nocco A, Tagliamacco A, Sementa A, Ceriolo P, Ghio L, Zecca M, Cardillo M, Garibotto G, Ghiggeri GM, Poli F. Posttransplant de novo donor-specific hla antibodies identify pediatric kidney recipients at risk for late antibody-mediated rejection. Am J Transplant. 2012 Dec;12(12):3355-62. doi: 10.1111/j.1600-6143.2012.04251.x. Epub 2012 Sep 7.

  PMID: 22959074 RESULT

• Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, Goldberg A, Birk PE, Rush DN, Nickerson PW. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant. 2012 May;12(5):1157-67. doi: 10.1111/j.1600-6143.2012.04013.x. Epub 2012 Mar 19.

  PMID: 22429309 RESULT

• Everly MJ, Rebellato LM, Haisch CE, Ozawa M, Parker K, Briley KP, Catrou PG, Bolin P, Kendrick WT, Kendrick SA, Harland RC, Terasaki PI. Incidence and impact of de novo donor-specific alloantibody in primary renal allografts. Transplantation. 2013 Feb 15;95(3):410-7. doi: 10.1097/TP.0b013e31827d62e3.

  PMID: 23380861 RESULT

• Hidalgo LG, Campbell PM, Sis B, Einecke G, Mengel M, Chang J, Sellares J, Reeve J, Halloran PF. De novo donor-specific antibody at the time of kidney transplant biopsy associates with microvascular pathology and late graft failure. Am J Transplant. 2009 Nov;9(11):2532-41. doi: 10.1111/j.1600-6143.2009.02800.x.

  PMID: 19843031 RESULT

• Wiebe C, Gibson IW, Blydt-Hansen TD, Pochinco D, Birk PE, Ho J, Karpinski M, Goldberg A, Storsley L, Rush DN, Nickerson PW. Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody. Am J Transplant. 2015 Nov;15(11):2921-30. doi: 10.1111/ajt.13347. Epub 2015 Jun 10.

  PMID: 26096305 RESULT

• Cooper JE, Gralla J, Chan L, Wiseman AC. Clinical significance of post kidney transplant de novo DSA in otherwise stable grafts. Clin Transpl. 2011:359-64.

  PMID: 22755431 RESULT

• DeVos JM, Patel SJ, Burns KM, Dilioglou S, Gaber LW, Knight RJ, Gaber AO, Land GA. De novo donor specific antibodies and patient outcomes in renal transplantation. Clin Transpl. 2011:351-8.

  PMID: 22755430 RESULT

• de Kort H, Willicombe M, Brookes P, Dominy KM, Santos-Nunez E, Galliford JW, Chan K, Taube D, McLean AG, Cook HT, Roufosse C. Microcirculation inflammation associates with outcome in renal transplant patients with de novo donor-specific antibodies. Am J Transplant. 2013 Feb;13(2):485-92. doi: 10.1111/j.1600-6143.2012.04325.x. Epub 2012 Nov 21.

  PMID: 23167441 RESULT

• Sharma A, Lewis JR, Lim WH, Palmer S, Strippoli G, Chapman JR, Alexander SI, Craig JC, Wong G. Renal transplant outcomes and de novo donor-specific anti-human leukocyte antigen antibodies: a systematic review. Nephrol Dial Transplant. 2018 Aug 1;33(8):1472-1480. doi: 10.1093/ndt/gfy077.

  PMID: 29660004 RESULT

• O'Leary JG, Samaniego M, Barrio MC, Potena L, Zeevi A, Djamali A, Cozzi E. The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients. Transplantation. 2016 Jan;100(1):39-53. doi: 10.1097/TP.0000000000000869.

  PMID: 26680372 RESULT

• Pratschke J, Dragun D, Hauser IA, Horn S, Mueller TF, Schemmer P, Thaiss F. Immunological risk assessment: The key to individualized immunosuppression after kidney transplantation. Transplant Rev (Orlando). 2016 Apr;30(2):77-84. doi: 10.1016/j.trre.2016.02.002. Epub 2016 Feb 18.

  PMID: 26965071 RESULT

• Smith JM, Martz K, Blydt-Hansen TD. Pediatric kidney transplant practice patterns and outcome benchmarks, 1987-2010: a report of the North American Pediatric Renal Trials and Collaborative Studies. Pediatr Transplant. 2013 Mar;17(2):149-57. doi: 10.1111/petr.12034. Epub 2013 Jan 2.

  PMID: 23281637 RESULT

• Filler G, Lepage N. To what extent does the understanding of pharmacokinetics of mycophenolate mofetil influence its prescription. Pediatr Nephrol. 2004 Sep;19(9):962-5. doi: 10.1007/s00467-004-1571-4. Epub 2004 Jul 15.

  PMID: 15257455 RESULT

• Le Meur Y, Buchler M, Thierry A, Caillard S, Villemain F, Lavaud S, Etienne I, Westeel PF, Hurault de Ligny B, Rostaing L, Thervet E, Szelag JC, Rerolle JP, Rousseau A, Touchard G, Marquet P. Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation. Am J Transplant. 2007 Nov;7(11):2496-503. doi: 10.1111/j.1600-6143.2007.01983.x. Epub 2007 Oct 1.

  PMID: 17908276 RESULT

• Tonshoff B, David-Neto E, Ettenger R, Filler G, van Gelder T, Goebel J, Kuypers DR, Tsai E, Vinks AA, Weber LT, Zimmerhackl LB. Pediatric aspects of therapeutic drug monitoring of mycophenolic acid in renal transplantation. Transplant Rev (Orlando). 2011 Apr;25(2):78-89. doi: 10.1016/j.trre.2011.01.001. Epub 2011 Mar 30.

  PMID: 21454065 RESULT

• Le Meur Y, Borrows R, Pescovitz MD, Budde K, Grinyo J, Bloom R, Gaston R, Walker RG, Kuypers D, van Gelder T, Kiberd B. Therapeutic drug monitoring of mycophenolates in kidney transplantation: report of The Transplantation Society consensus meeting. Transplant Rev (Orlando). 2011 Apr;25(2):58-64. doi: 10.1016/j.trre.2011.01.002. Epub 2011 Mar 30. No abstract available.

  PMID: 21454067 RESULT

• Pawinski T, Hale M, Korecka M, Fitzsimmons WE, Shaw LM. Limited sampling strategy for the estimation of mycophenolic acid area under the curve in adult renal transplant patients treated with concomitant tacrolimus. Clin Chem. 2002 Sep;48(9):1497-504.

  PMID: 12194926 RESULT

• Magee JC, Krishnan SM, Benfield MR, Hsu DT, Shneider BL. Pediatric transplantation in the United States, 1997-2006. Am J Transplant. 2008 Apr;8(4 Pt 2):935-45. doi: 10.1111/j.1600-6143.2008.02172.x.

  PMID: 18336697 RESULT

• Chen B, Gu Z, Chen H, Zhang W, Fen X, Cai W, Fan Q. Establishment of high-performance liquid chromatography and enzyme multiplied immunoassay technology methods for determination of free mycophenolic acid and its application in Chinese liver transplant recipients. Ther Drug Monit. 2010 Oct;32(5):653-60. doi: 10.1097/FTD.0b013e3181f01397.

  PMID: 20814351 RESULT

• Filler G, Todorova EK, Bax K, Alvarez-Elias AC, Huang SH, Kobrzynski MC. Minimum mycophenolic acid levels are associated with donor-specific antibody formation. Pediatr Transplant. 2016 Feb;20(1):34-8. doi: 10.1111/petr.12637. Epub 2015 Nov 21.

  PMID: 26589470 RESULT

• Metzger RA, Delmonico FL, Feng S, Port FK, Wynn JJ, Merion RM. Expanded criteria donors for kidney transplantation. Am J Transplant. 2003;3 Suppl 4:114-25. doi: 10.1034/j.1600-6143.3.s4.11.x. No abstract available.

  PMID: 12694055 RESULT

• Mallon DH, Summers DM, Bradley JA, Pettigrew GJ. Defining delayed graft function after renal transplantation: simplest is best. Transplantation. 2013 Nov 27;96(10):885-9. doi: 10.1097/TP.0b013e3182a19348.

  PMID: 24056620 RESULT

• Czyzewski L, Wyzgal J, Czyzewska E, Kurowski A, Sierdzinski J, Labus A, Truszewski Z, Szarpak L. Performance of the MDRD, CKD-EPI, and Cockcroft-Gault Formulas in Relation to Nutritional Status in Stable Renal Transplant Recipients. Transplant Proc. 2016 Jun;48(5):1494-7. doi: 10.1016/j.transproceed.2016.01.083.

  PMID: 27496434 RESULT

• Malheiro J, Tafulo S, Dias L, Martins LS, Fonseca I, Beirao I, Castro-Henriques A, Cabrita A. Analysis of preformed donor-specific anti-HLA antibodies characteristics for prediction of antibody-mediated rejection in kidney transplantation. Transpl Immunol. 2015 Mar;32(2):66-71. doi: 10.1016/j.trim.2015.01.002. Epub 2015 Feb 7.

  PMID: 25661873 RESULT

• Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D, Nankivell BJ, Halloran PF, Colvin RB, Akalin E, Alachkar N, Bagnasco S, Bouatou Y, Becker JU, Cornell LD, Duong van Huyen JP, Gibson IW, Kraus ES, Mannon RB, Naesens M, Nickeleit V, Nickerson P, Segev DL, Singh HK, Stegall M, Randhawa P, Racusen L, Solez K, Mengel M. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 2018 Feb;18(2):293-307. doi: 10.1111/ajt.14625. Epub 2018 Jan 21.

  PMID: 29243394 RESULT

• van Gelder T, Silva HT, de Fijter JW, Budde K, Kuypers D, Tyden G, Lohmus A, Sommerer C, Hartmann A, Le Meur Y, Oellerich M, Holt DW, Tonshoff B, Keown P, Campbell S, Mamelok RD. Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration-controlled trial. Transplantation. 2008 Oct 27;86(8):1043-51. doi: 10.1097/TP.0b013e318186f98a.

  PMID: 18946341 RESULT

MeSH Terms

Conditions

Delayed Graft Function

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Wujun Xue, Prof.

  First Affiliated Hospital Xi'an Jiaotong University

  STUDY CHAIR

Central Study Contacts

Wujun Xue, Prof.

CONTACT

+86 13991990128; xwujun163@mail.xjtu.edu.cn

Jin Zheng, Prof.

CONTACT

+86 18133916118; jzheng@mail.xjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: To estimate the incidence of DSA formation during 12-months post-transplantation

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 24, 2020
• Study Start: January 22, 2021
• Primary Completion: December 21, 2022
• Study Completion: December 31, 2023
• Last Updated: May 27, 2022

Record last verified: 2022-04

Locations

CN (1)