Ignite Creation Date:
2025-12-25 @ 4:40 AM
Ignite Modification Date:
2026-03-05 @ 6:13 AM
Study NCT ID:
NCT03702218
Status:
WITHDRAWN
Last Update Posted:
2023-05-06
First Post:
2018-10-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Hepatitis C Positive Donor Into Hepatitis C Negative Recipients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006526', 'term': 'Hepatitis C'}], 'ancestors': [{'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D006525', 'term': 'Hepatitis, Viral, Human'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D018178', 'term': 'Flaviviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D006505', 'term': 'Hepatitis'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'never started', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2019-07-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-07', 'completionDateStruct': {'date': '2019-07-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-05-04', 'studyFirstSubmitDate': '2018-10-08', 'studyFirstSubmitQcDate': '2018-10-08', 'lastUpdatePostDateStruct': {'date': '2023-05-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-10-11', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-07-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'SVR after receiving an organ from a donor previously exposed to Hepatitis C after treatment direct-acting antiviral drugs.', 'timeFrame': '12 months', 'description': 'To improve access to transplantation with use of HCV-non viremic and HCV-viremic organs in HCV negative patients'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Transplantation', 'Hepatitis C'], 'conditions': ['Hepatitis C']}, 'referencesModule': {'references': [{'pmid': '27438538', 'type': 'BACKGROUND', 'citation': 'Goldberg DS, Blumberg E, McCauley M, Abt P, Levine M. Improving Organ Utilization to Help Overcome the Tragedies of the Opioid Epidemic. Am J Transplant. 2016 Oct;16(10):2836-2841. doi: 10.1111/ajt.13971. Epub 2016 Aug 24.'}, {'pmid': '29205441', 'type': 'BACKGROUND', 'citation': 'Bari K, Luckett K, Kaiser T, Diwan T, Cuffy M, Schoech MR, Safdar K, Blackard JT, Apewokin S, Paterno F, Sherman KE, Zucker SD, Anwar N, Shah SA. Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C liver transplant recipients. Hepatology. 2018 May;67(5):1673-1682. doi: 10.1002/hep.29704. Epub 2018 Mar 26.'}]}, 'descriptionModule': {'briefSummary': 'Despite many efforts to increase the size of the donor pool, there is a large and growing disparity between the number of donor kidneys and livers available for transplantation and the number of patients on the transplant waiting list. New donor pools are needed to satisfy the lack of available donor organs, along with expanded criteria for the existing donor pools.\n\nA new standard of care now exists at most local and regional transplant centers. This new standard of care is based on the use of multiple direct-acting antiviral agents (DAAs) for treatment of hepatitis C virus (HCV) that have been approved by the Food and Drug Administration (FDA) for the treatment of hepatitis C and are associated with high HCV cure rates and minimal side effect profiles. The efficacy and tolerability of these medications has allowed the expansion of the available donor pool by making HCV antibody positive non viremic organs and HCV-viremic organs (when HCV is detectable in the blood) available to HCV-naive recipients on the organ transplantation waiting list. Expansion of this donor pool may decrease time on the waiting list and improve quality of life and survival while waiting for organ transplantation.\n\nStudy Aim:\n\nWe propose a clinical protocol to utilize solid organs from exposed and/or HCV-viremic organ donors for transplantation into HCV negative recipients.\n\nThe primary purpose of the clinical protocol is to:\n\nCollect prospective standard of care laboratory data on the results of these interventions', 'detailedDescription': "Once the donor is accepted for transplantation and the recipient enrolled in the innovative clinical practice, donor HCV Ab status will be requested to initiate HCV RNA viral load testing.\n\nDonor data will be recorded as per our standard practice and as mandated by UNOS. Our University of Maryland Medical Center team will be responsible for the donor operation as per standard of care.\n\nHep C Ab + NAT - Donor to Naïve Recipient This group will be monitored as illustrated in figure 1. Hep C Ab+ NAT+ Donor to Naïve Recipient HCV RNA levels, liver biochemistries, and renal function will be measured 3 days after transplant. HCV Genotype will be determined after HCV RNA is \\>1,000 IU/mL. HCV RNA levels will be measured weekly after transplant until HCV treatment is initiated.\n\nDue to risk of HBV reactivation with DAA therapy, Hepatitis B surface antigen, surface antibody and core antibody status will be determined prior to HCV therapy. In patients with a prior exposure to HBV (i.e. positive HBV core antibody), Hepatitis B surface antigen levels will be monitored throughout therapy.\n\nAll patients will be seen in the Hepatology clinic within 4 weeks of transplant to establish care and follow-up.\n\nHCV Therapy DAA therapy will be prescribed to all patients according to AASLD and IDSA joint guidelines, after giving consideration to the transplanted organ, renal function, and HCV genotype. All regimens exclude administration of ribavirin.\n\nTherapy will be initiated as soon as possible (pending initiation of oral intake and insurance approval) following organ transplantation.\n\nDAAs will be prescribed, after which medications will then be delivered to the patient's home or to the bedside.\n\nIf therapy is delayed beyond the 4-week appointment with Hepatology post-transplant, a protocol to monitor for infection, new-onset diabetes mellitus, glomerulonephritis and severe cholestatic hepatitis will be implemented. This protocol will include weekly blood work to include: CBC with differential, hepatic function panel, basic metabolic panel, and coagulation studies.\n\nLiver Transplant:\n\n• Combinations of choice:\n\n* Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6\n* Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR\\>30\n* Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR\\>30\n\nKidney Transplant:\n\n• Combinations of choice:\n\n* Mavyret (glecaprevir/pibrentasvir) - genotype 1-6\n* Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR\\>30 HCV Follow-Up HCV RNA, complete blood count (CBC) and liver biochemistries will be checked 4 weeks, 8 weeks, and 12 weeks after starting therapy. In patients previously exposed to HBV, HBV surface antigen will be followed qualitatively at the same intervals.\n\nHCV RNA will also be checked 12 weeks after completion of therapy to define cure, or sustained virologic response. As part of long-term follow-up, HCV RNA will be checked annually at routine post-transplant visits.\n\nIf SVR is not achieved, a second, and if needed, third antiviral regimen will be provided to the participant at no cost.\n\nTransplant, Post-Operative, Immunosuppression Follow Up All will be as per UMMC standard of care. Unless otherwise contraindicated, tacrolimus immune suppression will be favored, due to drug-drug interactions associated with DATs and cyclosporine."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* RECIPIENT INCLUSION CRITERIA\n\n * Patients undergoing solid organ transplantation, including liver, kidney, and simultaneous liver-kidney who are not chronically infected with HCV\n * No evident contraindication for organ transplantation\n * HCV RNA negative (can be isolated HCV antibody positive provided the patient will have no history of previously treated HCV)\n * Age 18-75 years at the time of transplantation\n * Signed Informed Consent Form\n * No identified living organ donor\n * Able to travel to the University of Maryland for routine post-transplant and HCV follow-up visits\n * Men and women must agree to use at least one barrier method to prevent any secretion exchange\n * No active illicit drug use\n\nDONOR INCLUSION CRITERIA\n\n• Qualitative HCV nucleic acid test (NAT) positive and/or Hepatitis C antibody positive HCV donors offered to the University of Maryland.\n\nExclusion Criteria:\n\nRECIPIENT EXCLUSION CRITERIA\n\n* History of prior solid organ transplantation\n* HIV infection\n* HBV surface antigen or DNA positive. Organs from HCV positive donors who are also Hepatitis B core antibody positive (hepatitis B surface antigen negative) can be used. These patients will however need to undergo prophylaxis for HBV according to their respective organ specific criteria and during treatment for hepatitis C due to the increased risk of reactivation of hepatitis B with DAA therapy\n* Waitlisted for a multi-organ transplant (with the exception of simultaneous liver-kidney transplant)\n* HCV RNA positive (can be isolated HCV antibody positive provided the patient will have no history of previously treated HCV)\n* Prior direct-acting antiviral (DAA) treatment for HCV. Patients previously treated with interferon-based regimens may be included.\n\nDONOR EXCLUSION CRITERIA\n\n* Every donor that is considered unsuitable by the transplant surgeon for any reason.\n* Hepatocellular carcinoma\n* HIV infection\n* Use of HCV positive livers to be determined according to current existing criteria'}, 'identificationModule': {'nctId': 'NCT03702218', 'briefTitle': 'Hepatitis C Positive Donor Into Hepatitis C Negative Recipients', 'organization': {'class': 'OTHER', 'fullName': 'University of Maryland, Baltimore'}, 'officialTitle': 'An Open-label Pilot Study to Determine the Safety and Efficacy of Hepatitis C Uninfected Recipients of Renal and Liver Transplants From a Currently Infected or Previously Infected Hepatitis C Donor', 'orgStudyIdInfo': {'id': 'HP-00083009'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Hep C Ab + NAT - Donor to Naïve Recipient', 'description': 'HCV Ab and HCV NAT testing at 3 days, week 1, week 2 and monthly for 3 months, at 6 months and 1 year. In approximately 16% of the patients, active hepatis C infection will ensue. For these patients, treatment is as follows.\n\nLiver Transplant:\n\n• Combinations of choice:\n\n* Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6\n* Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR\\>30\n* Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR\\>30\n\nKidney Transplant:\n\n• Combinations of choice:\n\n* Mavyret (glecaprevir/pibrentasvir) - genotype 1-6\n* Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR\\>30', 'interventionNames': ['Drug: Direct Acting Antivirals']}, {'type': 'EXPERIMENTAL', 'label': 'Hep C Ab+ NAT+ Donor to Naïve Recipient', 'description': 'HCV RNA levels, liver biochemistries, and renal function will be measured 3 days after transplant. HCV Genotype will be determined after HCV RNA is \\>1,000 IU/mL. HCV RNA levels will be measured weekly after transplant until HCV treatment is initiated.\n\nLiver Transplant:\n\n• Combinations of choice:\n\n* Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6\n* Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR\\>30\n* Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR\\>30\n\nKidney Transplant:\n\n• Combinations of choice:\n\n* Mavyret (glecaprevir/pibrentasvir) - genotype 1-6\n* Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR\\>30', 'interventionNames': ['Drug: Direct Acting Antivirals']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Hep C Ab- NAT - Donor to Naïve Recipient', 'description': 'Current standard of care for donor recipient infectious disease matching. No treatment necessary', 'interventionNames': ['Drug: Direct Acting Antivirals']}], 'interventions': [{'name': 'Direct Acting Antivirals', 'type': 'DRUG', 'description': 'Patients who are given organ transplants from donors that are Ab positive and NAT negative or Ab positive and NAT positive for Hepatitis C will be treated with direct acting antivirals after transplant if they become NAT+ for hepatitis C.\n\nInterventions as follows.\n\nLiver Transplant:\n\n• Combinations of choice:\n\n* Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6\n* Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR\\>30\n* Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR\\>30\n\nKidney Transplant:\n\n• Combinations of choice:\n\n* Mavyret (glecaprevir/pibrentasvir) - genotype 1-6\n* Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR\\>30', 'armGroupLabels': ['Hep C Ab + NAT - Donor to Naïve Recipient', 'Hep C Ab+ NAT+ Donor to Naïve Recipient', 'Hep C Ab- NAT - Donor to Naïve Recipient']}]}, 'contactsLocationsModule': {'locations': [{'zip': '21201', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'University of Maryland Medical Center', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}]}, 'ipdSharingStatementModule': {'infoTypes': ['SAP'], 'ipdSharing': 'YES', 'description': 'Results will be published in peer reviewed journals.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Maryland, Baltimore', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}