Utilization of Hepatitis C Positive Kidneys in Negative Recipients

Hepatitis C Clinical Trial

Official title:

An Open Label, Proof of Concept Study to Evaluate the Feasibility and Safety of Kidney Transplant From HCV Positive Donors Into HCV Negative Recipient

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03801707
• Other study ID #: 2018H0499
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 22, 2019
• Est. completion date: April 30, 2021

Study information

• Verified date: August 2023
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety and feasibility of transplanting kidneys from Hepatitis C virus (HCV) infected donors into recipients without HCV infection

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: April 30, 2021
• Est. primary completion date: April 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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%

• Estimated post-transplant survival (EPTS) index >20% and <80%

• Negative pre-transplant human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) serology and blood HCV polymerase chain reaction (PCR)

• No clinically significant pre-transplant liver disease

Exclusion Criteria:

• Living donor available

• Dialysis time >5 years

• Listing for multi-organ transplantation

• Active or recent history (<6 months) of alcohol abuse or substance abuse

• Clinically significant liver disease as determined by principal investigator

• History of hepatocarcinoma

• Pregnancy or lactation

• Refusal to accept blood transfusion

• 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%

Related Conditions & MeSH terms

• HCV
• Hepatitis
• Hepatitis A
• Hepatitis C
• Kidney Transplant

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	Brenda Cuson	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	12 weeks
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.	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.	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.	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.	12 months

External Links

•   USRDS Annual Data Report 2017