The Effect of Steroid Pulse Therapy for the Reduction of Acute Rejection Episode in Subclinical Borderline Changes

NCT02664493 | Unknown DMC

• 1 other identifier: 2015-10-017-002
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

• Several studies have shown that about 30% of transplanted kidneys with stable function present with tubule-interstitial mononuclear cell infiltration in protocol biopsies and therefore meet criteria for acute rejection. This subclinical rejection (SCR) has also been correlated with subsequent chronic allograft nephropathy and allograft dysfunction.
• The Banff scheme defines the minimal threshold for acute T-cell mediated rejection as infiltration of 25% or more of the renal cortex with five or more mononuclear cells in a focus of tubulitis or intimal arteritis (histological indices i2t2 or v1) and refers to borderline changes as those with insufficient for a diagnosis of acute T-cell mediated rejection, including mild to moderate (\<50%) cortical infiltration and one to four mononuclear cells per tubule in cross section (i1t1 or i2t1)
• No consensus for the treating patients with borderline changes has been reached. Borderline changes with graft dysfunction are occasionally routinely treated with steroid pulse and, whereas subclinical borderline changes are simply 'ignored'. Particularly, a previous study demonstrated that most cases designated borderline by histopathology are found to be non-rejection by molecular phenotyping
• The aim of this study is to investigate the effect of early steroid pulse therapy for the reduction of acute rejection episode during the first year after renal transplantation in the patients who will show subclinical borderline changes at 2-week protocol biopsy.

Conditions

Chronic Renal Failure

Keywords

kidney transplantation; subclinical borderline rejection; steroid pulse therapy

Outcome Measures

Primary Outcomes (1)

• The reduction of acute rejection episode during the first year after renal transplantation in the patients who will show subclinical borderline changes at 2-week protocol biopsy.

  1 year

Secondary Outcomes (2)

• Persistent subclinical rejection and chronic graft nephropathy at 1 year protocol biopsy

  1 year

• The effect of early steroid pulse therapy on the opportunistic infection including bacterial, fungal, and viral infections.

  1 year

Study Arms (2)

SPT group

EXPERIMENTAL

The patients who will show borderline change in 2-week protocol biopsy with stable graft function will be included in this study. Methylprednisolone 0.5 g daily for 3 days will be administered in (Steroid pulse therapy) SPT group.

Drug: Methylprednisolone

non-SPT group

NO INTERVENTION

The patients who will show borderline change in 2-week protocol biopsy with stable graft function will be included in this study. Steroid pulse therapy (SPT) will not be applied and no additional treatment will be added in non-SPT group

Interventions

Methylprednisolone DRUG

Steroid pulse therapy : Methylprednisolone 0.5 g daily for 3 days, followed by a tapered dose of 60 mg per day for a period of five days.

Also known as: high dose steroid therapy

SPT group

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patients who fulfill all the following conditions
• Age 19 - 70 years.
• The patients who underwent renal transplantation.
• The patients who will show borderline change in 2-week protocol biopsy with stable graft function will be included in this study.
• (Stable function is defined as serum creatinine ≤1.5 mg/dl and ≤15% increase in serum creatinine in the 2 weeks before biopsy.)

You may not qualify if:

• The patients who had clinical uremic symptom within 2 weeks after kidney transplantation..
• The patients who had elevated serum creatinine level more than 1.5mg/dl or 15% compared to previous result.
• The patients' age under 19 years or over 70 years.
• The patients who underwent preoperative desensitization.
• The patients who had multiple organ transplantation.
• The patients who showed an allergic reaction to steroid.
• The patients who had psychologic disease (eg. depression) or history of psychologic medication.
• The patients participated in another clinical trial within 30 days before this study.
• The patients who did not agree with a consent form.

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung medical center

Seoul, South Korea

RECRUITING

Related Publications (8)

• Rush DN, Henry SF, Jeffery JR, Schroeder TJ, Gough J. Histological findings in early routine biopsies of stable renal allograft recipients. Transplantation. 1994 Jan;57(2):208-11. doi: 10.1097/00007890-199401001-00009.

  PMID: 8310509 RESULT

• Miyagi M, Ishikawa Y, Mizuiri S, Aikawa A, Ohara T, Hasegawa A. Significance of subclinical rejection in early renal allograft biopsies for chronic allograft dysfunction. Clin Transplant. 2005 Aug;19(4):456-65. doi: 10.1111/j.1399-0012.2005.00303.x.

  PMID: 16008588 RESULT

• Legendre C, Thervet E, Skhiri H, Mamzer-Bruneel MF, Cantarovich F, Noel LH, Kreis H. Histologic features of chronic allograft nephropathy revealed by protocol biopsies in kidney transplant recipients. Transplantation. 1998 Jun 15;65(11):1506-9. doi: 10.1097/00007890-199806150-00020.

  PMID: 9645814 RESULT

• Furness PN, Kirkpatrick U, Taub N, Davies DR, Solez K. A UK-wide trial of the Banff classification of renal transplant pathology in routine diagnostic practice. Nephrol Dial Transplant. 1997 May;12(5):995-100. doi: 10.1093/ndt/12.5.995.

  PMID: 9175057 RESULT

• Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Hayry PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Yamaguchi Y, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999 Feb;55(2):713-23. doi: 10.1046/j.1523-1755.1999.00299.x.

  PMID: 9987096 RESULT

• Solez K, Axelsen RA, Benediktsson H, Burdick JF, Cohen AH, Colvin RB, Croker BP, Droz D, Dunnill MS, Halloran PF, et al. International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int. 1993 Aug;44(2):411-22. doi: 10.1038/ki.1993.259.

  PMID: 8377384 RESULT

• Nankivell BJ, Chapman JR. The significance of subclinical rejection and the value of protocol biopsies. Am J Transplant. 2006 Sep;6(9):2006-12. doi: 10.1111/j.1600-6143.2006.01436.x. Epub 2006 Jun 22.

  PMID: 16796717 RESULT

• de Freitas DG, Sellares J, Mengel M, Chang J, Hidalgo LG, Famulski KS, Sis B, Einecke G, Halloran PF. The nature of biopsies with "borderline rejection" and prospects for eliminating this category. Am J Transplant. 2012 Jan;12(1):191-201. doi: 10.1111/j.1600-6143.2011.03784.x. Epub 2011 Oct 12.

  PMID: 21992503 RESULT

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; 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

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Sung Joo Kim, Ph.D.

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kyo Won Lee, M.D.

CONTACT

+821099335192; kw1980.lee@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 27, 2016
• Study Start: February 1, 2016
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: April 6, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)