Ignite Creation Date:
2025-12-25 @ 4:57 AM
Ignite Modification Date:
2025-12-26 @ 3:57 AM
Study NCT ID:
NCT04917718
Status:
UNKNOWN
Last Update Posted:
2022-04-13
First Post:
2021-06-02
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Renal Tubular Injury and Transplant Outcomes in Cardiac Recipients Converting From IR Tacrolimus to XR Tacrolimus
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D051436', 'term': 'Renal Insufficiency, Chronic'}], 'ancestors': [{'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'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 42}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2021-08-16', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-04', 'completionDateStruct': {'date': '2024-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-04-12', 'studyFirstSubmitDate': '2021-06-02', 'studyFirstSubmitQcDate': '2021-06-02', 'lastUpdatePostDateStruct': {'date': '2022-04-13', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-06-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Urinary neutrophil gelatinase-associated lipocalin (NGAL)', 'timeFrame': '4 weeks', 'description': 'Change in Urinary NGAL level (ng/mL)'}], 'secondaryOutcomes': [{'measure': 'Estimated Glomerular Filtration Rate (eGFR)', 'timeFrame': '4 weeks', 'description': 'Change in eGRF level by the Creatinine-Cystatin C CKD-EPI equation (mL/min/1.73m2)'}, {'measure': 'Microalbuminuria', 'timeFrame': '4 weeks', 'description': 'Change in Urine albumin-creatinine ratio'}, {'measure': 'CYP3A5 expressor category', 'timeFrame': 'Baseline', 'description': 'CYP3A5 genotyping to determine expressor category'}, {'measure': 'Heart transplant rejection', 'timeFrame': '1 year', 'description': 'The rate of rejection as defined as treated rejection within the last 30 days for any grade\\>1R, AMR, or acute graft dysfunction (LVEF drop greater than 10%)'}, {'measure': 'Cardiac allograft vasculopathy', 'timeFrame': '1 year', 'description': 'The rate of cardiac allograft vasculopathy based on coronary angiography with or without IVUS and right heart catheterization hemodynamics'}, {'measure': 'Blood pressure', 'timeFrame': '1 year', 'description': 'Change in blood pressure (mmHg)'}, {'measure': 'Serum glucose', 'timeFrame': '1 year', 'description': 'Change in serum glucose levels (mg/dL)'}, {'measure': 'LDL Cholesterol', 'timeFrame': '1 year', 'description': 'Change in LDL cholesterol level (mg/dL)'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Immediate Release Tacrolimus', 'Extended Release Tacrolimus', 'IR Tacrolimus', 'XR Tacrolimus', 'Renal Tubular Injury', 'Heart Transplant Recipient', 'Chronic Kidney Disease'], 'conditions': ['Chronic Kidney Diseases', 'Heart Transplant']}, 'referencesModule': {'references': [{'pmid': '12954741', 'type': 'BACKGROUND', 'citation': 'Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, Arndorfer J, Christensen L, Merion RM. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003 Sep 4;349(10):931-40. doi: 10.1056/NEJMoa021744.'}, {'pmid': '19218475', 'type': 'BACKGROUND', 'citation': 'Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol. 2009 Feb;4(2):481-508. doi: 10.2215/CJN.04800908.'}, {'pmid': '11265958', 'type': 'BACKGROUND', 'citation': 'Camara NO, Matos AC, Rodrigues DA, Pereira AB, Pacheco-Silva A. Early detection of heart transplant patients with increased risk of ciclosporin nephrotoxicity. Lancet. 2001 Mar 17;357(9259):856-7. doi: 10.1016/S0140-6736(00)04207-0.'}, {'pmid': '6382005', 'type': 'BACKGROUND', 'citation': 'Myers BD, Ross J, Newton L, Luetscher J, Perlroth M. Cyclosporine-associated chronic nephropathy. N Engl J Med. 1984 Sep 13;311(11):699-705. doi: 10.1056/NEJM198409133111103.'}, {'pmid': '17318073', 'type': 'BACKGROUND', 'citation': 'Cosio FG, Amer H, Grande JP, Larson TS, Stegall MD, Griffin MD. Comparison of low versus high tacrolimus levels in kidney transplantation: assessment of efficacy by protocol biopsies. Transplantation. 2007 Feb 27;83(4):411-6. doi: 10.1097/01.tp.0000251807.72246.7d.'}, {'pmid': '29162334', 'type': 'BACKGROUND', 'citation': 'Trofe-Clark J, Brennan DC, West-Thielke P, Milone MC, Lim MA, Neubauer R, Nigro V, Bloom RD. Results of ASERTAA, a Randomized Prospective Crossover Pharmacogenetic Study of Immediate-Release Versus Extended-Release Tacrolimus in African American Kidney Transplant Recipients. Am J Kidney Dis. 2018 Mar;71(3):315-326. doi: 10.1053/j.ajkd.2017.07.018. Epub 2017 Nov 20.'}, {'pmid': '23279614', 'type': 'BACKGROUND', 'citation': 'Bunnapradist S, Ciechanowski K, West-Thielke P, Mulgaonkar S, Rostaing L, Vasudev B, Budde K; MELT investigators. Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial. Am J Transplant. 2013 Mar;13(3):760-9. doi: 10.1111/ajt.12035. Epub 2012 Dec 21.'}, {'pmid': '30576367', 'type': 'BACKGROUND', 'citation': 'Chancharoenthana W, Leelahavanichkul A, Wattanatorn S, Avihingsanon Y, Praditpornsilpa K, Eiam-Ong S, Townamchai N. Alteration of urinary neutrophil gelatinase-associated lipocalin as a predictor of tacrolimus-induced chronic renal allograft fibrosis in tacrolimus dose adjustments following kidney transplantation. PLoS One. 2018 Dec 21;13(12):e0209708. doi: 10.1371/journal.pone.0209708. eCollection 2018.'}, {'pmid': '20458318', 'type': 'BACKGROUND', 'citation': 'Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S, Muniappa N, Thudium D, Gerhold D, Holder DJ, Bobadilla NA, Marrer E, Perentes E, Cordier A, Vonderscher J, Maurer G, Goering PL, Sistare FD, Bonventre JV. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol. 2010 May;28(5):478-85. doi: 10.1038/nbt.1623.'}, {'pmid': '25329716', 'type': 'BACKGROUND', 'citation': 'Tsuchimoto A, Shinke H, Uesugi M, Kikuchi M, Hashimoto E, Sato T, Ogura Y, Hata K, Fujimoto Y, Kaido T, Kishimoto J, Yanagita M, Matsubara K, Uemoto S, Masuda S. Urinary neutrophil gelatinase-associated lipocalin: a useful biomarker for tacrolimus-induced acute kidney injury in liver transplant patients. PLoS One. 2014 Oct 20;9(10):e110527. doi: 10.1371/journal.pone.0110527. eCollection 2014.'}]}, 'descriptionModule': {'briefSummary': 'Immediate release (IR) tacrolimus peaks in the first two hours after administration. These peak levels are influenced by CYP3A5 expression with expressors requiring higher total daily doses with higher peak levels compared to non-expressors. Tacrolimus XR (Envarsus) is a once daily formulation with delayed absorption and lower peak levels while maintaining similar trough levels as seen with IR tacrolimus. A randomized trial of conversion from IR tacrolimus to tacrolimus XR in kidney transplant recipients have shown similar efficacy and adverse events between the two groups but no improvement in estimated GFR. However, urinary biomarkers of acute kidney injury associated with changes in tacrolimus dosing may be more sensitive then serum creatinine. The objective of this study is to assess renal tubular injury in heart transplant recipients who are converted from immediate release to tacrolimus XR. The hypothesis is that the delayed absorption and lower peak levels of tacrolimus XR will lead to less tubular injury and improved renal function without increased risk to the heart allograft.', 'detailedDescription': 'The primary outcome is change in urinary NGAL expression with conversion from IR tacrolimus to tacrolimus XR. In aim 1, changes in urinary biomarkers of tubular injury at 4 weeks after conversion to tacrolimus XR with stable trough levels will be assessed. These changes will be assessed by CYP3A5 expressor category that will be determined by genotyping of a single gene for variants. The changes in GFR using the creatinine-cystatin C CKD-EPI equation will be assessed. In aim 2, the rate of rejection as defined as treated rejection within the last 30 days for any grade \\> 1R or AMR or acute graft dysfunction (LV ejection fraction drop \\> 10%) will be looked. The cardiac allograft vasculopathy based on coronary angiography +/- IVUS and right heart catheterization hemodynamics at baseline and 1 year post conversion will also be evaluated. In addition to changes in cardiac function, the changes in blood pressure, serum glucose, and cholesterol in the first year after conversion will be assessed.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Stable, heart-only transplant recipient within 10 years of transplantation\n* 18 -80 years old\n* Currently taking IR Tacrolimus\n* Baseline eGFR\\> 30mL/min/1.73m2\n\nExclusion Criteria:\n\n* Multiple organ transplant recipients\n* Less than 18 years old\n* Greater than 80 years old\n* Heart-only transplants recipients with active malignancy, rejection, or greater than 10 years from transplantation'}, 'identificationModule': {'nctId': 'NCT04917718', 'briefTitle': 'Renal Tubular Injury and Transplant Outcomes in Cardiac Recipients Converting From IR Tacrolimus to XR Tacrolimus', 'organization': {'class': 'OTHER', 'fullName': 'Loyola University'}, 'officialTitle': 'Assessment of Renal Tubular Injury and Transplant Outcomes in Cardiac Recipients Converting From Immediate Release Tacrolimus to Extended Release Tacrolimus.', 'orgStudyIdInfo': {'id': '212781'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Extended Release Tacrolimus', 'description': 'All participants who consent to the study will be in this group.', 'interventionNames': ['Drug: Conversion from IR Tacrolimus to XR Tacrolimus']}], 'interventions': [{'name': 'Conversion from IR Tacrolimus to XR Tacrolimus', 'type': 'DRUG', 'description': 'All participants will be consented to the study on IR Tacrolimus. After their baseline visit, they will be converted to XR Tacrolimus', 'armGroupLabels': ['Extended Release Tacrolimus']}]}, 'contactsLocationsModule': {'locations': [{'zip': '60153', 'city': 'Maywood', 'state': 'Illinois', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'Loyola University Medical Center', 'geoPoint': {'lat': 41.8792, 'lon': -87.84312}}], 'centralContacts': [{'name': 'Sanjeev Akkina, MD', 'role': 'CONTACT', 'email': 'sanjeev.akkina@lumc.edu', 'phone': '708-327-4897'}], 'overallOfficials': [{'name': 'Sanjeev Akkina, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Loyola University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Loyola University', 'class': 'OTHER'}, 'collaborators': [{'name': 'Veloxis Pharmaceuticals', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD, Associate Professor of Medicine', 'investigatorFullName': 'Sanjeev Akkina', 'investigatorAffiliation': 'Loyola University'}}}}