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出境医 / 临床实验 / The Use of Hepatitis C Positive Kidneys in Hepatitis C Negative Kidney Transplant Recipients

The Use of Hepatitis C Positive Kidneys in Hepatitis C Negative Kidney Transplant Recipients

Study Description
Brief Summary:
This is an open-label, pilot trial to test the safety and efficacy of transplantation of kidneys from hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the kidney transplant waitlist. Treatment and prophylaxis will be administered using a transmission-triggered approach for the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later scenario (HCV Ab+/NAT+ donors, arm 2).

Condition or disease Intervention/treatment Phase
Kidney Transplantation Hepatitis C Drug: sofosbuvir/velpatasvir Phase 2

Detailed Description:

This is a prospective, single center, pilot, open-label study of transplantation of kidneys of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir (Epclusa®). Recipients of a kidney from HCVAb+/NAT- donors will be in arm 1 (the transmission-triggered arm) of the study. In this arm, the study will monitor HCV by measuring HCV RNA in renal transplant recipients. If HCV RNA is detected, indicating transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12 weeks. Virological response will be assessed at 4 weeks, end of treatment and 12 weeks after completion of therapy.

Recipients of a kidney from HCVAb+/NAT+ donors will be in arm 2 (the prophylaxis arm) of the study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir (Epclusa®) immediately post-operatively and will undergo close monitoring of HCV RNA for evidence of transmission.

To be eligible for the study, subjects need to be listed for renal transplantation, be not infected with HCV, HBV or HIV, and sign informed consent.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Transplantation of Kidneys of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa)
Actual Study Start Date : May 29, 2019
Estimated Primary Completion Date : May 1, 2024
Estimated Study Completion Date : May 1, 2024
Arms and Interventions
Arm Intervention/treatment
Experimental: HCV seropositive non-viremic (HCV Ab+/NAT-) donor

Kidney recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated.

Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).

 Drug: sofosbuvir/velpatasvir
12-week, oral, fixed-dose
Other Name: Epclusa
Experimental: HCV seropositive viremic (HCV Ab+/NAT+) donor
Starting post-operative day 1, kidney recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).
 Drug: sofosbuvir/velpatasvir
12-week, oral, fixed-dose
Other Name: Epclusa
Outcome Measures
Primary Outcome Measures :
  1. Adverse Events [ Time Frame: 5 years ]
    Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group

  2. HCV free at 1 year [ Time Frame: 1 year ]
    Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation


Secondary Outcome Measures :
  1. Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients [ Time Frame: 5 years ]
  2. Incidence of allograft rejection [ Time Frame: 5 years ]
  3. Incidence of graft loss [ Time Frame: 5 years ]
  4. All-cause mortality [ Time Frame: 5 years ]
  5. Waitlist time after enrollment [ Time Frame: 5 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria (recipients):

  1. Patients with end-stage renal disease listed for kidney transplantation at UPMC.
  2. On chronic hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate < 15 ml/min
  3. Age ≥ 18
  4. No available living kidney donor
  5. Listed for an isolated kidney transplant at UPMC with <60m of accrued transplant waiting time and/or <60m of dialysis time
  6. Have panel reactive antibody level of <98%
  7. No obvious contraindication to kidney transplant
  8. Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation
  9. Able to provide informed consent
  10. Be willing to use a contraceptive method for a year after transplant

Exclusion criteria (recipients):

  1. HIV positive
  2. HCVAb or HCV RNA positive
  3. Presence of behavioral risk factors for contracting HCV other than being on hemodialysis. These behavioral risk factors are current injection drug use, current intranasal illicit drug use, current percutaneous/parenteral exposures in an unregulated setting.
  4. Hepatitis B surface antigen positive
  5. History of liver cirrhosis
  6. Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months
  7. History of atrial fibrillation requiring the use of amiodarone over the past 12m
  8. Patients with etiology of renal failure with increased risk of causing early graft failure as assessed by the investigator team
  9. Receipt of prior organ transplant
  10. Waitlisted for a multi-organ transplant
  11. Pregnant women
  12. Known allergy to sofosbuvir/velpatasvir
  13. Any condition, psychiatric or physical, that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study

Inclusion criteria (donors):

  1. HCV antibody positive
  2. HCV NAT negative or positive
  3. Kidney donor profile index (KDPI) score <85

Exclusion criteria (donors):

  1. Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT)
  2. Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT)
  3. Known ongoing therapy for HCV
Contacts and Locations

Locations
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United States, Pennsylvania
UPMC
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Amit D Tevar, MD
University of Pittsburgh Medical Center
Investigators
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Principal Investigator: Amit Tevar, MD University of Pittsburgh
Study Director: Fernanda Silviera, MD University of Pittsburgh
Tracking Information
First Submitted Date  ICMJE January 15, 2019
First Posted Date  ICMJE January 18, 2019
Last Update Posted Date November 5, 2020
Actual Study Start Date  ICMJE May 29, 2019
Estimated Primary Completion Date May 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2019)
  • Adverse Events [ Time Frame: 5 years ]
    Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group
  • HCV free at 1 year [ Time Frame: 1 year ]
    Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2019)
  • Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients [ Time Frame: 5 years ]
  • Incidence of allograft rejection [ Time Frame: 5 years ]
  • Incidence of graft loss [ Time Frame: 5 years ]
  • All-cause mortality [ Time Frame: 5 years ]
  • Waitlist time after enrollment [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Use of Hepatitis C Positive Kidneys in Hepatitis C Negative Kidney Transplant Recipients
Official Title  ICMJE Transplantation of Kidneys of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa)
Brief Summary This is an open-label, pilot trial to test the safety and efficacy of transplantation of kidneys from hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the kidney transplant waitlist. Treatment and prophylaxis will be administered using a transmission-triggered approach for the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later scenario (HCV Ab+/NAT+ donors, arm 2).
Detailed Description

This is a prospective, single center, pilot, open-label study of transplantation of kidneys of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir (Epclusa®). Recipients of a kidney from HCVAb+/NAT- donors will be in arm 1 (the transmission-triggered arm) of the study. In this arm, the study will monitor HCV by measuring HCV RNA in renal transplant recipients. If HCV RNA is detected, indicating transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12 weeks. Virological response will be assessed at 4 weeks, end of treatment and 12 weeks after completion of therapy.

Recipients of a kidney from HCVAb+/NAT+ donors will be in arm 2 (the prophylaxis arm) of the study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir (Epclusa®) immediately post-operatively and will undergo close monitoring of HCV RNA for evidence of transmission.

To be eligible for the study, subjects need to be listed for renal transplantation, be not infected with HCV, HBV or HIV, and sign informed consent.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Kidney Transplantation
  • Hepatitis C
Intervention  ICMJE Drug: sofosbuvir/velpatasvir
12-week, oral, fixed-dose
Other Name: Epclusa
Study Arms  ICMJE
  • Experimental: HCV seropositive non-viremic (HCV Ab+/NAT-) donor

    Kidney recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated.

    Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).

    Intervention: Drug: sofosbuvir/velpatasvir
  • Experimental: HCV seropositive viremic (HCV Ab+/NAT+) donor
    Starting post-operative day 1, kidney recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).
    Intervention: Drug: sofosbuvir/velpatasvir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: January 15, 2019) 		60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2024
Estimated Primary Completion Date May 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria (recipients):

  1. Patients with end-stage renal disease listed for kidney transplantation at UPMC.
  2. On chronic hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate < 15 ml/min
  3. Age ≥ 18
  4. No available living kidney donor
  5. Listed for an isolated kidney transplant at UPMC with <60m of accrued transplant waiting time and/or <60m of dialysis time
  6. Have panel reactive antibody level of <98%
  7. No obvious contraindication to kidney transplant
  8. Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation
  9. Able to provide informed consent
  10. Be willing to use a contraceptive method for a year after transplant

Exclusion criteria (recipients):

  1. HIV positive
  2. HCVAb or HCV RNA positive
  3. Presence of behavioral risk factors for contracting HCV other than being on hemodialysis. These behavioral risk factors are current injection drug use, current intranasal illicit drug use, current percutaneous/parenteral exposures in an unregulated setting.
  4. Hepatitis B surface antigen positive
  5. History of liver cirrhosis
  6. Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months
  7. History of atrial fibrillation requiring the use of amiodarone over the past 12m
  8. Patients with etiology of renal failure with increased risk of causing early graft failure as assessed by the investigator team
  9. Receipt of prior organ transplant
  10. Waitlisted for a multi-organ transplant
  11. Pregnant women
  12. Known allergy to sofosbuvir/velpatasvir
  13. Any condition, psychiatric or physical, that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study

Inclusion criteria (donors):

  1. HCV antibody positive
  2. HCV NAT negative or positive
  3. Kidney donor profile index (KDPI) score <85

Exclusion criteria (donors):

  1. Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT)
  2. Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT)
  3. Known ongoing therapy for HCV
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03809533
Other Study ID Numbers  ICMJE PRO18030039
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: We do not plan to share individual patient data outside of our investigative team. Aggregate data will be shared in publications as appropriate.
Responsible Party Amit D Tevar, MD, University of Pittsburgh
Study Sponsor  ICMJE Amit D Tevar, MD
Collaborators  ICMJE University of Pittsburgh Medical Center
Investigators  ICMJE
Principal Investigator: Amit Tevar, MD University of Pittsburgh
Study Director: Fernanda Silviera, MD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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