Testing Immunosuppression Threshold in Renal Allografts To Extend eGFR

NCT02581436 | Completed

• 1 other identifier: 1217
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the addition of "Kidney Solid Organ Rejection Test" (kSORT), in the clinical follow-up of renal transplant recipients, compared to clinical standard surveillance in the first two years after kidney transplantation. The design of the study is a partially blinded, randomized control trial of patients with living and deceased donor. The recruitment will be in a third level attention hospital in Mexico city (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán). The main outcomes are the rate and grade of acute rejection, histologic chronic index of the one year protocol biopsy and glomerular filtration rate.

Conditions

Disorder Related to Renal Transplantation; Renal Transplant Rejection; Acute Graft Rejection

Keywords

Prediction test; genetic transcription profile; Transplant follow-up; Chronic index; Graft Function

Outcome Measures

Primary Outcomes (3)

• Incidence and grade of biopsy-proven acute rejection

  Based in BANFF 2013 classification, of allograft biopsies obtained during the study period

  two years

• Chronic index in one year protocol biopsy

  interstitial fibrosis, tubular atrophy and chronic histomorphometry parameters

  One year

• Calculated glomerular filtration rate

  Calculated glomerular filtration rate with MDRD-IDMS formula

  One and two years

Secondary Outcomes (8)

• Describe the behavior of the assay throughout the follow-up period.

  Two years

• Determine the impact of time with positive or negative kSORT assays on the main outcomes

  two years

• Describe the behavior of the assay after the maneuver of increasing or tapering immunosuppression and after treatment of acute rejection.

  Two years

• Establish the sensitivity and specificity of the kSORT assay in the detection of acute rejection

  Two years

• Analyze gene expression relating to renal tissue inflammation and fibrosis at the time of the one-year protocol biopsy, and their relation to clinical variables including the previous and current kSORT assay results.

  One year

Other Outcomes (2)

• Immunosuppression dosage, levels and brands

  Two years

• Population genetics

  Two years

Study Arms (2)

kSORT assay based follow-up

EXPERIMENTAL

Post Transplant surveillance based on the result of the kSORT assay.

Other: kSORT assay based follow-up

Standard follow-up

ACTIVE COMPARATOR

Post Transplant surveillance based on standard of care.

Other: Standard follow-up

Interventions

kSORT assay based follow-up OTHER

kSORT assay in pre-established days: 14, 45, 90, 180, 365 and 540 of post transplantation follow-up. If kSORT result is positive maintenance immunosuppressive will be increased (tacrolimus trough levels 12-15 ng/mL, Mofetil Mycophenolate 1.5 mg every 24 hours and prednisone 5 mg/day) and graft biopsy will be obtained. Kidney biopsy will be obtained one mo after treatment as well as kSORT assay. If kSORT result is negative, the maintenance immunosuppressor dosages will remain as established in our institutional guidelines. If after a year of follow-up, the kSORT result is negative, immunosuppression will be decreased (Tacrolimus levels 5 - 10 ng/ml and mofetil mycophenolate 500 mg every 12 hours).

kSORT assay based follow-up

Standard follow-up OTHER

Surveillance will be the usual, includes creatinine determinations and clinical evaluation as often as established in the institutional protocol. A kidney graft biopsy will be obtained in case of dysfunction (increase in serum creatinine \>25% above baseline or 0.3 mg/mL above baseline) or as part of our institutional programmed biopsies (months 3 and 12). Treatment will be established in accordance with biopsy results. In all cases of rejection a kidney biopsy will be obtained one month after initiating treatment. In this control group, samples for kSORT analysis will be collected on pre-established dates for the study, but patient treatment will not be contingent on the assay's results; investigators will be blinded to the result in this control patient group.

Standard follow-up

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Kidney transplant recipients from living or deceased donor from National Institute of Health and Nutrition Salvador Zubirán

You may not qualify if:

• Kidney transplant recipients who have contraindication to graft biopsy. (coagulopathy, anticoagulant therapy or double antiaggregation)

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead
• University of California, San Francisco: collaborator

Study Sites (1)

National Institute of Medical Sciences and Health Salvador Zubiran

Mexico City, D.F., 14040, Mexico

Location

Related Publications (6)

• Thierry A, Thervet E, Vuiblet V, Goujon JM, Machet MC, Noel LH, Rioux-Leclercq N, Comoz F, Cordonnier C, Francois A, Marcellin L, Girardot-Seguin S, Touchard G. Long-term impact of subclinical inflammation diagnosed by protocol biopsy one year after renal transplantation. Am J Transplant. 2011 Oct;11(10):2153-61. doi: 10.1111/j.1600-6143.2011.03695.x. Epub 2011 Aug 22.

  PMID: 21883902 BACKGROUND

• Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012 Feb;12(2):388-99. doi: 10.1111/j.1600-6143.2011.03840.x. Epub 2011 Nov 14.

  PMID: 22081892 RESULT

• Meier-Kriesche HU, Ojo AO, Hanson JA, Cibrik DM, Punch JD, Leichtman AB, Kaplan B. Increased impact of acute rejection on chronic allograft failure in recent era. Transplantation. 2000 Oct 15;70(7):1098-100. doi: 10.1097/00007890-200010150-00018.

  PMID: 11045649 RESULT

• Pallardo Mateu LM, Sancho Calabuig A, Capdevila Plaza L, Franco Esteve A. Acute rejection and late renal transplant failure: risk factors and prognosis. Nephrol Dial Transplant. 2004 Jun;19 Suppl 3:iii38-42. doi: 10.1093/ndt/gfh1013.

  PMID: 15192134 RESULT

• Li L, Khatri P, Sigdel TK, Tran T, Ying L, Vitalone MJ, Chen A, Hsieh S, Dai H, Zhang M, Naesens M, Zarkhin V, Sansanwal P, Chen R, Mindrinos M, Xiao W, Benfield M, Ettenger RB, Dharnidharka V, Mathias R, Portale A, McDonald R, Harmon W, Kershaw D, Vehaskari VM, Kamil E, Baluarte HJ, Warady B, Davis R, Butte AJ, Salvatierra O, Sarwal MM. A peripheral blood diagnostic test for acute rejection in renal transplantation. Am J Transplant. 2012 Oct;12(10):2710-8. doi: 10.1111/j.1600-6143.2012.04253.x.

  PMID: 23009139 RESULT

• Roedder S, Sigdel T, Salomonis N, Hsieh S, Dai H, Bestard O, Metes D, Zeevi A, Gritsch A, Cheeseman J, Macedo C, Peddy R, Medeiros M, Vincenti F, Asher N, Salvatierra O, Shapiro R, Kirk A, Reed EF, Sarwal MM. The kSORT assay to detect renal transplant patients at high risk for acute rejection: results of the multicenter AART study. PLoS Med. 2014 Nov 11;11(11):e1001759. doi: 10.1371/journal.pmed.1001759. eCollection 2014 Nov.

  PMID: 25386950 RESULT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2015
• First Posted: October 21, 2015
• Study Start: September 1, 2014
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: March 6, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)