Ignite Creation Date:
2025-12-24 @ 9:34 PM
Ignite Modification Date:
2026-01-05 @ 6:37 PM
Study NCT ID:
NCT01473732
Status:
TERMINATED
Last Update Posted:
2018-10-16
First Post:
2011-11-14
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068338', 'term': 'Everolimus'}, {'id': 'D016559', 'term': 'Tacrolimus'}, {'id': 'D009173', 'term': 'Mycophenolic Acid'}], 'ancestors': [{'id': 'D020123', 'term': 'Sirolimus'}, {'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D002208', 'term': 'Caproates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D005227', 'term': 'Fatty Acids'}, {'id': 'D008055', 'term': 'Lipids'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'eakalin@montefiore.org', 'phone': '718-920-4815', 'title': 'Dr. Enver Akalin, Medical Director Kidney Transplant', 'organization': 'Montefiore Medical Center'}, 'certainAgreement': {'piSponsorEmployee': True, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'The only two patients enrolled in everolimus group did not complete the study due to events leading to death and one due to proteinuria. The first participant was enrolled in March of 2012 and the study was terminated in August 2012.', 'description': 'The two patients enrolled in everolimus group did not complete the study due to events leading to death and one due to proteinuria discontinued everolimus and switched to tacrolimus. The death occurred two months after enrollment. The proteinuria event occurred fours months after enrollment. No patient enrolled in reduced tacrolimus dose group and due to difficulty in enrollment the study is terminated. No data was analyzed for any participant.', 'eventGroups': [{'id': 'EG000', 'title': 'Everolimus (Zortress)+ Mycophenolic Acid(Myfortic)', 'description': 'Everolimus: Starting dose 1.5 mg bid, target trough level 6-10 ng/ml. Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Both for one year.', 'otherNumAtRisk': 2, 'deathsNumAtRisk': 2, 'otherNumAffected': 0, 'seriousNumAtRisk': 2, 'deathsNumAffected': 1, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Reduced Dose Prograf+ Mycophenolic Acid(Myfortic)', 'description': 'Tacrolimus: Target trough level of Tacrolimus 3-5 ng/ml. Myfortic Min. 360 mg bid and Max. 720 mg bid Both for one year.', 'otherNumAtRisk': 0, 'deathsNumAtRisk': 0, 'otherNumAffected': 0, 'seriousNumAtRisk': 0, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'seriousEvents': [{'term': 'proteinuria', 'notes': 'proteinuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 2, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 0, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Small bowel obstruction leading to death', 'notes': 'Small bowel obstruction lead to sepsis which lead to death', 'stats': [{'groupId': 'EG000', 'numAtRisk': 2, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 0, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change in eGFR (Creatinine Clearance) as Measured by Serum Creatinine Blood Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Everolimus (Zortress)+ Mycophenolic Acid(Myfortic)', 'description': 'Everolimus: Starting dose 1.5 mg bid, target trough level 6-10 ng/ml. Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Both for one year.'}, {'id': 'OG001', 'title': 'Reduced Dose Prograf+ Mycophenolic Acid(Myfortic)', 'description': 'Tacrolimus: Target trough level of Tacrolimus 3-5 ng/ml. Myfortic Min. 360 mg bid and Max. 720 mg bid Both for one year.'}], 'timeFrame': 'Baseline, One year', 'description': 'Estimated glomerular filtration rate (eGFR) indicates kidney function. Normal eGFR value for healthy is 80-120ml/min. For transplants, it is expected to be 60-80 ml/min.', 'reportingStatus': 'POSTED', 'populationDescription': 'The only two patients enrolled did not reach the one year mark; they did not complete the study so there was no data to analyze.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Everolimus (Zortress)+ Mycophenolic Acid(Myfortic)', 'description': 'Everolimus: Starting dose 1.5 mg bid, target trough level 6-10 ng/ml. Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Both for one year.'}, {'id': 'FG001', 'title': 'Reduced Dose Prograf+ Mycophenolic Acid(Myfortic)', 'description': 'Tacrolimus: Target trough level of Tacrolimus 3-5 ng/ml. Myfortic Min. 360 mg bid and Max. 720 mg bid Both for one year.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Everolimus (Zortress)+ Mycophenolic Acid(Myfortic)', 'description': 'Everolimus: Starting dose 1.5 mg bid, target trough level 6-10 ng/ml. Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Both for one year.'}, {'id': 'BG001', 'title': 'Reduced Dose Prograf+ Mycophenolic Acid(Myfortic)', 'description': 'Tacrolimus: Target trough level of Tacrolimus 3-5 ng/ml. Myfortic Min. 360 mg bid and Max. 720 mg bid Both for one year.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '63', 'spread': '2', 'groupId': 'BG000'}, {'value': '63', 'spread': '2', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'We did not analyze the data due to no patient enrolled in reduced dose prograf group and 2 patients enrolled in everolimus group did not complete the study due to death and adverse event'}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 2}}, 'statusModule': {'whyStopped': 'terminated after 2 patients due to difficulty in enrollment', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2012-03', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-09', 'completionDateStruct': {'date': '2012-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-09-17', 'studyFirstSubmitDate': '2011-11-14', 'resultsFirstSubmitDate': '2018-06-11', 'studyFirstSubmitQcDate': '2011-11-16', 'lastUpdatePostDateStruct': {'date': '2018-10-16', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-08-20', 'studyFirstPostDateStruct': {'date': '2011-11-17', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-09-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2012-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in eGFR (Creatinine Clearance) as Measured by Serum Creatinine Blood Test', 'timeFrame': 'Baseline, One year', 'description': 'Estimated glomerular filtration rate (eGFR) indicates kidney function. Normal eGFR value for healthy is 80-120ml/min. For transplants, it is expected to be 60-80 ml/min.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['CNI toxicity', 'CAI'], 'conditions': ['Chronic Allograft Injury', 'Calcineurin Inhibitor Toxicity']}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to find out how well the current drug regimen (including low Prograf dose and Myfortic, which is usually recommended to prevent any further deterioration in the kidney function) works and how safe it is when compared to a combination of Zortress and Myfortic in patients with chronic kidney injury associated with Prograf or Neoral use.', 'detailedDescription': 'Specific Aim 1: To investigate allograft and peripheral blood cell gene expression patterns of patients with CAI by using Affymetrix microarrays.\n\nHypothesis 1: Gene expression patterns of patients with biopsy findings suggesting calcineurin inhibitor (CNI) toxicity without significant tubulointerstitial infiltrates or transplant glomerulopathy might demonstrate upregulation of genes related to tissue injury, fibrosis, and extracellular matrix deposition without upregulation of genes related to alloimmune response, such as, T and/or B lymphocyte activation markers, surface receptors, co-stimulation molecules, adhesion molecules, cytokines, and chemokines comparing to patients with significant tubulointerstitial infiltrates and/or transplant glomerulopathy that might show upregulation of genes related to alloimmune response, such as, T and/or B lymphocyte activation markers, surface receptors, co-stimulation molecules, adhesion molecules, cytokines, and chemokines.\n\nSpecific Aim 2: The effect of everolimus (Zortress)/ mycophenolate sodium (EC-MPS, myfortic®) treatment on allograft and peripheral gene expression patterns.\n\nHypothesis 2: Everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) treatment attenuates the progression of CAI due to CNI toxicity by downregulating the expression of genes related to fibrosis, such as, transforming growth factor-β, thrombospondin 1, and platelet derived growth factor-C.\n\nSpecific Aim 3: To document the clinical outcomes of everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) in patients with CAI due to CNI toxicity Hypothesis 3: Everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) can attenuate the progression of CAI due to CNI toxicity and may improve the creatinine clearance.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nAll patients with biopsy proven pure chronic allograft injury due to CNI toxicity.\n\nExclusion Criteria:\n\n1. 24 hour urine protein or spot urine protein/creatinine ratio \\> 500 mg/day\n2. Estimated glomerular filtration rate (eGFR) \\< 30 ml/min by modification of Diet in Renal Disease( MDRD) or 24 hour urine collection\n3. Patients with Donor-specific antibody (DSA) by Luminex (mean fluorescence intensity values \\> 1,000)\n4. Recipients of multiple organ transplants or ABO-incompatible allograft\n5. Current panel reactive antibody (PRA) greater than 30 percent\n6. Graft loss at randomization\n7. Pregnant women\n8. Previous history of acute rejection\n9. Previous history of allergy or intolerance to Zortress or Myfortic\n10. Platelet count less than 100,000\n11. White Blood Cell (WBC) less than 3,000\n12. Hb less than 9 g/dL or Htc less than 30%\n13. Biopsy findings of\n\n * Chronic antibody mediated rejection\n * Acute rejection\n * Positive C4d staining\n * Interstitial infiltrates more than 25% of the area\n * Transplant glomerulopathy\n * Recurrent or de novo glomerular disease\n * Polyoma nephropathy or positive simian virus 40 (SV40) staining'}, 'identificationModule': {'nctId': 'NCT01473732', 'briefTitle': 'Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity', 'organization': {'class': 'OTHER', 'fullName': 'Montefiore Medical Center'}, 'officialTitle': 'Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity', 'orgStudyIdInfo': {'id': '11-05-196'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Everolimus (Zortress)', 'interventionNames': ['Drug: Everolimus', 'Drug: Mycophenolic acid']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Reduced dose Tacrolimus (Prograf)', 'interventionNames': ['Drug: Tacrolimus', 'Drug: Mycophenolic acid']}], 'interventions': [{'name': 'Everolimus', 'type': 'DRUG', 'otherNames': ['Zortress'], 'description': 'Starting dose 1.5 mg bid, target trough level 6-10 ng/ml.', 'armGroupLabels': ['Everolimus (Zortress)']}, {'name': 'Tacrolimus', 'type': 'DRUG', 'otherNames': ['Prograf'], 'description': 'Target trough level of Tacrolimus 3-5 ng/ml.', 'armGroupLabels': ['Reduced dose Tacrolimus (Prograf)']}, {'name': 'Mycophenolic acid', 'type': 'DRUG', 'otherNames': ['Myfortic'], 'description': 'Myfortic Min. dose 360 mg bid and Max dose 720 mg bid. Used in both arms. Used for one year.', 'armGroupLabels': ['Everolimus (Zortress)', 'Reduced dose Tacrolimus (Prograf)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10467', 'city': 'The Bronx', 'state': 'New York', 'country': 'United States', 'facility': 'Montefiore Medical Center', 'geoPoint': {'lat': 40.84985, 'lon': -73.86641}}], 'overallOfficials': [{'name': 'Enver Akalin, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Montefiore Medical Center/AECOM'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Montefiore Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Prof. Dept of Medicine (Nephrology)', 'investigatorFullName': 'Enver Akalin', 'investigatorAffiliation': 'Montefiore Medical Center'}}}}