Utilization of Hepatitis C Positive Kidneys in Negative Recipients
Study Details
Study Description
Brief Summary
To evaluate the safety and feasibility of transplanting kidneys from Hepatitis C virus (HCV) infected donors into recipients without HCV infection
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
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
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Intervention group kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies. |
Drug: Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]
fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C
Other Names:
Drug: Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]
Three tablets once a day for 12 weeks for treatment of hepatitis C
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients with undetectable HCV polymerase chain reaction (PCR) at 12 weeks after completion of HCV treatment with Sofosbuvir/Velpatasvir [12 weeks]
Efficacy
- The incidence of adverse events related to Sofosbuvir/Velpatasvir drug therapy [12 weeks]
safety
Secondary Outcome Measures
- Estimated glomerular filtration rate (eGFR) at 6 and 12 months post-transplant [6 and 12 months]
Safety
- Patient's survival at 6 and 12 months [6 and 12 months]
Safety
- Graft survival at 12 months [12 months]
Safety
Eligibility Criteria
Criteria
Recipient Inclusion/Exclusion Criteria:
Inclusion Criteria:
-
Adult age >18 years able to provide consent
-
Lack of available living donor
-
Calculated pre-transplant reactive panel (cPRA) of <80%
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Estimated post-transplant survival (EPTS) index >20% and <80%
-
Negative pre-transplant human immunodeficiency virus (HIV), HCV, and hepatitis B virus (HBV) serology and blood HCV PCR
-
No clinically significant pre-transplant liver disease
Exclusion Criteria:
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Living donor available
-
Dialysis time >5 years
-
Listing for multi-organ transplantation
-
Active or recent history (<6 months) of alcohol abuse or substance abuse
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Clinically significant liver disease as determined by principal investigator
-
History of hepatocarcinoma
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Pregnancy or lactation
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Refusal to accept blood transfusion
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HIV infection
-
HCV pcr or antibody positive
-
HBV infection
Donor Inclusion Criteria:
-
Positive HCV PCR at time of donation
-
Kidney donor profile index (KDPI)<85%
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Brenda Cuson | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- Ohio State University
Investigators
- Principal Investigator: Reem Daloul, MD, Ohio State University School of Biomedical Science: The Ohio State University College of Medicine
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Agarwal K, Castells L, Müllhaupt B, Rosenberg WMC, McNabb B, Arterburn S, Camus G, McNally J, Stamm LM, Brainard DM, Mani Subramanian G, Mariño 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.
- 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.
- 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.
- Feld JJ, Jacobson IM, Hézode 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.
- 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.
- Foster GR, Afdhal N, Roberts SK, Bräu N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourlière 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.
- 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 1:18-113. doi: 10.1111/ajt.14557.
- 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.
- Younossi ZM, Stepanova M, Sulkowski M, Foster GR, Reau N, Mangia A, Patel K, Bräu 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.
- 2018H0499