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To evaluate the safety and feasibility of transplanting kidneys from Hepatitis C virus (HCV) infected donors into recipients without HCV infection
This will be an open label, prospective, interventional, proof of concept study to evaluate the feasibility and safety of kidney transplant from HCV positive donors into HCV negative recipients using treatment with pan-genotypic direct acting antiviral therapies (DAAS) for treatment of post-transplant HCV transmission
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention group | Experimental | kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sofosbuvir / Velpatasvir Oral Tablet [Epclusa] | Drug | fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients With Undetectable Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) at 12 Weeks After Completion of HCV Treatment | Proportion of patients with undetectable hepatitis C virus (HCV) polymerase chain reaction (PCR) at 12 weeks after completion of HCV treatment was to test the efficacy of the treatment. | 12 weeks |
| Elevation in Liver Enzyme >5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies | Elevation in liver enzyme >5 times the upper limits, development of acute cholestatic hepatitis , or intolerance to Direct acting antiviral therapies was to test the safety of utilizing HepC positive kidneys for transplant. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant | Estimated glomerular filtration rate (eGFR) at 6 and 12 months post-transplant was to test the safety of utilizing of HepC positive kidneys. | 6 and 12 months |
| Patient's Survival at 6 and 12 Months |
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Recipient Inclusion/Exclusion Criteria:
Inclusion Criteria:
Exclusion Criteria:
Donor Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Reem Daloul, MD | Ohio State University School of Biomedical Science: The Ohio State University College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brenda Cuson | Columbus | Ohio | 43210 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29292608 | Background | Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Robinson A, Wainright JL, Haynes CR, Snyder JJ, Kasiske BL, Israni AK. OPTN/SRTR 2016 Annual Data Report: Kidney. Am J Transplant. 2018 Jan;18 Suppl 1(Suppl 1):18-113. doi: 10.1111/ajt.14557. | |
| 26569658 | Background | Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M; ASTRAL-4 Investigators. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015 Dec 31;373(27):2618-28. doi: 10.1056/NEJMoa1512614. Epub 2015 Nov 16. |
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In total 18 patients were removed from the study: 9 participants received hepatitis C virus nucleic antigen test (HCV NAT) negative kidney transplants, 8 participants were removed from the kidney transplant deceased waiting-list, and 1 participant died prior to receiving kidney transplant
54 Kidney transplant candidates were enrolled and listed on the Deceased Donor Kidney Wait-list to receive hepatitis C virus (HCV) viremic kidneys
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| ID | Title | Description |
|---|---|---|
| FG000 | Intervention Group | kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies. Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intervention Group | kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies. Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Patients With Undetectable Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) at 12 Weeks After Completion of HCV Treatment | Proportion of patients with undetectable hepatitis C virus (HCV) polymerase chain reaction (PCR) at 12 weeks after completion of HCV treatment was to test the efficacy of the treatment. | Posted | Count of Participants | Participants | 12 weeks |
|
25 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intervention Group | kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies. Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Liver enzyme elevation | Hepatobiliary disorders | Non-systematic Assessment | liver enzyme elevation > 5 upper normal limit occurred in two patients. one patient prior to initiation of direct acting antiviral therapy, one patient during recurrence of HCV viremia in the setting of resistant mutation |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brenda Cuson | The Ohio State University | 614-293-6883 | Brenda.Cuson@osumc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jan 14, 2022 | May 23, 2023 | Prot_SAP_ICF_001.pdf |
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| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| D000069474 | Sofosbuvir |
| C000604171 | velpatasvir |
| C000611331 | sofosbuvir-velpatasvir drug combination |
| C000612853 | glecaprevir |
| C000622691 | pibrentasvir |
| C000654128 | glecaprevir and pibrentasvir |
| ID | Term |
|---|---|
| D014542 | Uridine Monophosphate |
| D014500 | Uracil Nucleotides |
| D011742 | Pyrimidine Nucleotides |
| D011743 | Pyrimidines |
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| Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET] | Drug | Three tablets once a day for 12 weeks for treatment of hepatitis C |
|
|
Patient's survival at 6 and 12 months measuring safety of utilizing of HepC positive kidneys. |
| 6 and 12 months |
| Graft Survival at 6 and 12 Months | Graft survival at 6 and 12 months measuring safety of utilizing HepC positive kidneys. | 12 months |
| 26571066 | Background | Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16. |
| 26476290 | Background | Feld JJ, Moreno C, Trinh R, Tam E, Bourgeois S, Horsmans Y, Elkhashab M, Bernstein DE, Younes Z, Reindollar RW, Larsen L, Fu B, Howieson K, Polepally AR, Pangerl A, Shulman NS, Poordad F. Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12weeks. J Hepatol. 2016 Feb;64(2):301-307. doi: 10.1016/j.jhep.2015.10.005. Epub 2015 Oct 22. |
| 26575258 | Background | Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17. |
| 27444413 | Background | Younossi ZM, Stepanova M, Sulkowski M, Foster GR, Reau N, Mangia A, Patel K, Brau N, Roberts SK, Afdhal N, Nader F, Henry L, Hunt S. Ribavirin-Free Regimen With Sofosbuvir and Velpatasvir Is Associated With High Efficacy and Improvement of Patient-Reported Outcomes in Patients With Genotypes 2 and 3 Chronic Hepatitis C: Results From Astral-2 and -3 Clinical Trials. Clin Infect Dis. 2016 Oct 15;63(8):1042-1048. doi: 10.1093/cid/ciw496. Epub 2016 Jul 20. |
| 29886154 | Background | Agarwal K, Castells L, Mullhaupt B, Rosenberg WMC, McNabb B, Arterburn S, Camus G, McNally J, Stamm LM, Brainard DM, Mani Subramanian G, Marino Z, Dufour JF, Forns X. Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. J Hepatol. 2018 Sep;69(3):603-607. doi: 10.1016/j.jhep.2018.05.039. Epub 2018 Jun 8. |
| 29672891 | Background | Reau N, Kwo PY, Rhee S, Brown RS Jr, Agarwal K, Angus P, Gane E, Kao JH, Mantry PS, Mutimer D, Reddy KR, Tran TT, Hu YB, Gulati A, Krishnan P, Dumas EO, Porcalla A, Shulman NS, Liu W, Samanta S, Trinh R, Forns X. Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection. Hepatology. 2018 Oct;68(4):1298-1307. doi: 10.1002/hep.30046. Epub 2018 Jul 25. |
| 29507971 | Background | Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, Wesson R, Reyad A, Naqvi FF, Ostrander D, Sugarman J, Segev DL, Sulkowski M, Desai NM. Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Ann Intern Med. 2018 Apr 17;168(8):533-540. doi: 10.7326/M17-2871. Epub 2018 Mar 6. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Primary cause of end stage kidney diseaes | Count of Participants | Participants |
|
| Time on dialysis prior to transplant | Median | Inter-Quartile Range | months |
|
| Donor (D) -Recipient (R) Cytomegalovirus (CMV) status | Count of Participants | Participants |
|
| Insurance type | Count of Participants | Participants |
|
| Pre-Transplant Calculated Panel Reactive Antibody (cPRA) % | Median | Inter-Quartile Range | percent |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Elevation in Liver Enzyme >5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies | Elevation in liver enzyme >5 times the upper limits, development of acute cholestatic hepatitis , or intolerance to Direct acting antiviral therapies was to test the safety of utilizing HepC positive kidneys for transplant. | Posted | Count of Participants | Participants | 12 weeks |
|
|
|
| Secondary | Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant | Estimated glomerular filtration rate (eGFR) at 6 and 12 months post-transplant was to test the safety of utilizing of HepC positive kidneys. | Posted | Median | Inter-Quartile Range | ml/min/1.73m^2 | 6 and 12 months |
|
|
|
| Secondary | Patient's Survival at 6 and 12 Months | Patient's survival at 6 and 12 months measuring safety of utilizing of HepC positive kidneys. | Posted | Count of Participants | Participants | 6 and 12 months |
|
|
|
| Secondary | Graft Survival at 6 and 12 Months | Graft survival at 6 and 12 months measuring safety of utilizing HepC positive kidneys. | Posted | Count of Participants | Participants | 12 months |
|
|
|
| 0 |
| 30 |
| 0 |
| 30 |
| 2 |
| 30 |
|
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| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |
| No significant adverse effect reported |
|