Ignite Creation Date:
2025-12-25 @ 1:27 AM
Ignite Modification Date:
2026-01-21 @ 9:43 PM
Study NCT ID:
NCT02664493
Status:
UNKNOWN
Last Update Posted:
2016-04-06
First Post:
2016-01-14
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Effect of Steroid Pulse Therapy for the Reduction of Acute Rejection Episode in Subclinical Borderline Changes
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007676', 'term': 'Kidney Failure, Chronic'}], 'ancestors': [{'id': 'D051436', 'term': 'Renal Insufficiency, Chronic'}, {'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008775', 'term': 'Methylprednisolone'}], 'ancestors': [{'id': 'D011239', 'term': 'Prednisolone'}, {'id': 'D011246', 'term': 'Pregnadienetriols'}, {'id': 'D011245', 'term': 'Pregnadienes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 154}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2016-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-04', 'completionDateStruct': {'date': '2020-07', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2016-04-05', 'studyFirstSubmitDate': '2016-01-14', 'studyFirstSubmitQcDate': '2016-01-26', 'lastUpdatePostDateStruct': {'date': '2016-04-06', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2016-01-27', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2020-07', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '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.', 'timeFrame': '1 year'}], 'secondaryOutcomes': [{'measure': 'Persistent subclinical rejection and chronic graft nephropathy at 1 year protocol biopsy', 'timeFrame': '1 year', 'description': 'the rejection will be defined according to Banff criteria including borderline rejection.\n\nthe degree of chronic graft nephropathy will be calculated based on a chronic sum score of the sum of the Banff chronic indices (cg + ci + ct + cv).\n\nthe persistent subclinical rejection rate and the degree of chronic graft nephropahty according to the groups will be compared.'}, {'measure': 'The effect of early steroid pulse therapy on the opportunistic infection including bacterial, fungal, and viral infections.', 'timeFrame': '1 year', 'description': 'infection episodes will be recorded.\n\ncytomegalovirus (CMV), BK polyomavirus (BKV), varicella zoster virus (VZV), bacteria, fungus, TB, pneumocystis carinii infection will be included.\n\nrate of infection according to groups will be compared.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['kidney transplantation', 'subclinical borderline rejection', 'steroid pulse therapy'], 'conditions': ['Chronic Renal Failure']}, 'referencesModule': {'references': [{'pmid': '8310509', 'type': 'RESULT', 'citation': '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': '16008588', 'type': 'RESULT', 'citation': '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': '9645814', 'type': 'RESULT', 'citation': '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': '9175057', 'type': 'RESULT', 'citation': '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': '9987096', 'type': 'RESULT', 'citation': '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': '8377384', 'type': 'RESULT', 'citation': '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': '16796717', 'type': 'RESULT', 'citation': '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': '21992503', 'type': 'RESULT', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': "* 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.\n* 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)\n* 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\n* 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.", 'detailedDescription': "Background\n\nSeveral 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 (1). This subclinical rejection (SCR) has also been correlated with subsequent chronic allograft nephropathy and allograft dysfunction (2,3).\n\nThe Banff 97 working classification of renal allograft pathology was introduced to standardize the histological definition of acute allograft rejection and to guide treatment of renal transplant recipients (4,5). 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) (6).\n\nThe averaged prevalence of borderline SCR at 1-2 week is 24% (range 12-38%), at 1-2 months is 23% (range 21-27%), at 2-3 months is 23% (range 11-41%) and 1 year is 17% (range 7-44%) from selected studies (7). However, the pathogenic role of such limited cortical mononuclear infiltration is not well established and no consensus for the treating patients with borderline changes has been reached. In practice, 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 (8). Furthermore, some previous studies have shown that the risk of infection is higher in patients receiving high dose steroid (9-12), and a previous study suggested that the infection risk was increased, up to as 1.5-fold, in patients receiving steroid pulse therapy (SPT) for acute rejection (13).\n\nSome previous studies revealed that the graft survival rates with treated borderline SCR was 99.1% at 1-year, 95.1% at 5-years, and 93.7% at 10-years (14) and the graft survival rates with untreated borderline SCR was 90.9% at 1-year (15). However, there was no randomized controlled study on the effect of steroid pulse therapy in stable renal transplant recipients with subclinical borderline changes.\n\nPurpose\n\n* The reduction in risk of graft failure is the pivotal measure of effectiveness for evaluating immunosuppressive regimens for renal transplantation. However, because of the long follow-up periods and large sample size required for such an endpoint, randomized controlled trials of immunosuppressive therapies have mostly relied on the surrogate endpoints.\n* In our institution, since routine protocol biopsies are performed at 2 weeks, 1 year, and 2 years after renal transplantation, it is practically difficult that graft survival is used as an endpoint for randomized controlled trials.\n* From a meta-analysis for 31 observational studies (16), acute rejection was associated with an increased risk of graft loss risk ratios ranged from 1.2 - 10.5. Furthermore, chronic allograft nephropathy and graft survival is strongly correlated with acute rejection episode during the first year after renal transplantation (17,18).\n* Therefore, 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.\n* To evaluate the benefit over the risk, this study also investigates the effect of early steroid pulse therapy on the opportunistic infection including bacterial, fungal, and viral infections."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '19 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\nThe patients who fulfill all the following conditions\n\n* Age 19 - 70 years.\n* The patients who underwent renal transplantation.\n* The patients who will show borderline change in 2-week protocol biopsy with stable graft function will be included in this study.\n\n(Stable function is defined as serum creatinine ≤1.5 mg/dl and ≤15% increase in serum creatinine in the 2 weeks before biopsy.)\n\nExclusion Criteria:\n\n* The patients who had clinical uremic symptom within 2 weeks after kidney transplantation..\n* The patients who had elevated serum creatinine level more than 1.5mg/dl or 15% compared to previous result.\n* The patients' age under 19 years or over 70 years.\n* The patients who underwent preoperative desensitization.\n* The patients who had multiple organ transplantation.\n* The patients who showed an allergic reaction to steroid.\n* The patients who had psychologic disease (eg. depression) or history of psychologic medication.\n* The patients participated in another clinical trial within 30 days before this study.\n* The patients who did not agree with a consent form."}, 'identificationModule': {'nctId': 'NCT02664493', 'briefTitle': 'The Effect of Steroid Pulse Therapy for the Reduction of Acute Rejection Episode in Subclinical Borderline Changes', 'organization': {'class': 'OTHER', 'fullName': 'Samsung Medical Center'}, 'officialTitle': 'The Effect of Steroid Pulse Therapy for the Reduction of Acute Rejection Episode in Subclinical Borderline Changes: An Open-Label, Randomized Clinical Trial', 'orgStudyIdInfo': {'id': '2015-10-017-002'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'SPT group', 'description': 'The patients who will show borderline change in 2-week protocol biopsy with stable graft function will be included in this study.\n\nMethylprednisolone 0.5 g daily for 3 days will be administered in (Steroid pulse therapy) SPT group.', 'interventionNames': ['Drug: Methylprednisolone']}, {'type': 'NO_INTERVENTION', 'label': 'non-SPT group', 'description': 'The patients who will show borderline change in 2-week protocol biopsy with stable graft function will be included in this study.\n\nSteroid pulse therapy (SPT) will not be applied and no additional treatment will be added in non-SPT group'}], 'interventions': [{'name': 'Methylprednisolone', 'type': 'DRUG', 'otherNames': ['high dose steroid therapy'], 'description': '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.', 'armGroupLabels': ['SPT group']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Seoul', 'status': 'RECRUITING', 'country': 'South Korea', 'contacts': [{'name': 'Sung Joo Kim, Prof.', 'role': 'CONTACT', 'email': 'kmhyj111@gmail.com', 'phone': '010-9933-3476'}], 'facility': 'Samsung medical center', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}], 'centralContacts': [{'name': 'Kyo Won Lee, M.D.', 'role': 'CONTACT', 'email': 'kw1980.lee@gmail.com', 'phone': '+821099335192'}], 'overallOfficials': [{'name': 'Sung Joo Kim, Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Samsung Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Samsung Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Sung-Joo Kim', 'investigatorAffiliation': 'Samsung Medical Center'}}}}