ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03500315
Previous Study | Return to List | Next Study

HOPE in Action Prospective Multicenter, Clinical Trial of Deceased HIVD+ Kidney Transplants for HIV+ Recipients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03500315
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : September 24, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
The primary objective of this study is to determine if an HIV-infected deceased kidney donor (HIVD+) transplant is safe with regards to major transplant-related and HIV-related complications.

Condition or disease Intervention/treatment Phase
Hiv Other: HIV D+/R+ Not Applicable

Detailed Description:
This study will evaluate if receiving a kidney transplant from an HIV-infected deceased kidney donor is safe with regards to survival and major transplant-related and HIV-related complications compared to receiving a kidney from an HIV-uninfected deceased kidney donor (HIVD-). Those participants who have accepted an HIVD- organ will be randomized to be followed in the full study or followed in the nested observational group.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: HOPE in Action Prospective Multicenter, Clinical Trial of Deceased HIVD+ Kidney Transplants for HIV+ Recipients
Actual Study Start Date : April 19, 2018
Estimated Primary Completion Date : August 1, 2021
Estimated Study Completion Date : August 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: HIV D+/R+
HIV-infected individuals that accept an organ from an HIV-infected deceased donor - enrollment 80
Other: HIV D+/R+
Kidney from an HIV-infected deceased donor

No Intervention: HIV D-/R+
HIV-infected individuals that accept an organ from an HIV-uninfected deceased donor -enrollment 80
No Intervention: HIV D-/R+ (observational)
HIV-infected individuals that accept an organ from an HIV-uninfected deceased donor and randomized to observational group - enrollment 200



Primary Outcome Measures :
  1. Composite event, time to first death or graft failure or serious adverse event (SAE) or HIV breakthrough or opportunistic infection [ Time Frame: From date of transplant through administrative censorship at study completion, up to 4 years ]
    Time to first of any of the following events: death or graft failure or serious adverse event (SAE) or HIV breakthrough or opportunistic infection


Secondary Outcome Measures :
  1. Pre-transplant mortality [ Time Frame: From date of enrollment to date of transplant or death of any cause, whichever comes first, assessed up to 4 years ]
    Time to mortality while enrolled before transplant (survival framework)

  2. Graft failure [ Time Frame: From date of transplant through administrative censorship at study completion, up to 4 years ]
    Time to mortality or re-transplant or return to maintenance dialysis (survival framework)

  3. Rate of serious adverse events [ Time Frame: From date of transplant through graft failure or administrative censorship at study completion, up to year 4 ]
    Count of post-transplant serious adverse events per person-year as assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0

  4. 6-month acute rejection [ Time Frame: From date of transplant to end of month 6 ]
    Proportion of recipients who experience acute rejection as measured by biopsy using Banff 2015 criteria: Borderline changes: 'Suspicious' for acute T-cell mediated rejection.This category is used when no intimal arteritis is present, but there are foci of mild tubulitis (t1, t2, or t3) with minor interstitial infiltration (i0 or i1) or interstitial infiltration (i2, i3) with mild (t1) tubulitis. Acute T-cell mediated rejection:Grade from IA defined as cases with significant interstitial infiltration (>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2) to III defined as cases with 'transmural' arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3)

  5. 1-year acute rejection [ Time Frame: From date of transplant to end of year 1 ]
    Proportion of recipients who experience acute rejection as measured by biopsy using Banff 2015 criteria: Borderline changes: 'Suspicious' for acute T-cell mediated rejection.This category is used when no intimal arteritis is present, but there are foci of mild tubulitis (t1, t2, or t3) with minor interstitial infiltration (i0 or i1) or interstitial infiltration (i2, i3) with mild (t1) tubulitis. Acute T-cell mediated rejection:Grade from IA defined as cases with significant interstitial infiltration (>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2) to III defined as cases with 'transmural' arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3)

  6. Incidence of graft rejection [ Time Frame: From date of transplant through administrative censorship, up to 4 years ]
    Cumulative incidence of acute rejection (survival framework) as measured by biopsy using Banff 2015 criteria: Borderline changes: 'Suspicious' for acute T-cell mediated rejection.This category is used when no intimal arteritis is present, but there are foci of mild tubulitis (t1, t2, or t3) with minor interstitial infiltration (i0 or i1) or interstitial infiltration (i2, i3) with mild (t1) tubulitis. Acute T-cell mediated rejection:Grade from IA defined as cases with significant interstitial infiltration (>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2) to III defined as cases with 'transmural' arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3)

  7. Graft function - Proportion eGFR <60 mL/min/1.73 m2 [ Time Frame: 3 months post-transplant ]
    Proportion of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  8. Graft function - Proportion eGFR <60 mL/min/1.73 m2 [ Time Frame: 6 months post-transplant ]
    Proportion of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  9. Graft function - Proportion eGFR <60 mL/min/1.73 m2 [ Time Frame: 9 months post-transplant ]
    Proportion of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  10. Graft function - Proportion eGFR <60 mL/min/1.73 m2 [ Time Frame: 1 year post-transplant ]
    Proportion of transplant recipients with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  11. Graft function - Proportion eGFR <60 mL/min/1.73 m2 [ Time Frame: 2 years post-transplant ]
    Proportion of participants with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  12. Graft function - Proportion eGFR <60 mL/min/1.73 m2 [ Time Frame: 3 years post-transplant ]
    Proportion of participants with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) < 60 mL/min/1.73 m2

  13. Graft function -mean eGFR [ Time Frame: 3 months post-transplant ]
    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  14. Graft function-mean eGFR [ Time Frame: 6 months post-transplant ]
    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  15. Graft function-mean eGFR [ Time Frame: 9 months post-transplant ]
    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  16. Graft function-mean eGFR [ Time Frame: 1 year post-transplant ]
    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  17. Graft function-mean eGFR [ Time Frame: 2 years post-transplant ]
    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  18. Graft function-mean eGFR [ Time Frame: 3 years post-transplant ]
    Mean calculated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

  19. Graft function - slope eGFR [ Time Frame: From date of transplant to end of follow-up, up to 4 years ]
    The slope of glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) over time (longitudinal analysis)

  20. Incidence of non-HIV renal disease [ Time Frame: 6 months post-transplant ]
    Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. focal segmental glomerulosclerosis

  21. Incidence of non-HIV renal disease [ Time Frame: 1 year post-transplant ]
    Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. focal segmental glomerulosclerosis

  22. Incidence of HIV-related renal disease [ Time Frame: 6 months post-transplant ]
    Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. HIV-associated nephropathy

  23. Incidence of HIV-related renal disease [ Time Frame: 1 year post-transplant ]
    Cumulative incidence of non HIV-related renal disease as measured by biopsy, e.g. HIV-associated nephropathy

  24. Donor and recipient apolipoprotein L1 (APOL1) [ Time Frame: Baseline ]
    Proportion of transplant recipients with at least 1 apolipoprotein L1 (APOL1) risk variant in donor and recipient

  25. HIV infection of renal allografts [ Time Frame: 6 months post-transplant ]
    Proportion of recipients with HIV seen in laser capture microdissection of renal biopsy

  26. Trajectory of recipient plasma HIV RNA over time [ Time Frame: From date of transplant through end of follow-up, up to 4 years ]
    Analysis of repeated measures of plasma HIV RNA (longitudinal model)

  27. Trajectory of recipient Cluster of Differentiation (CD4) count over time [ Time Frame: From date of transplant through end of follow up, up to 4 years ]
    Analysis of repeated measures of Cluster of Differentiation 4 (CD4) count (longitudinal model)

  28. Incidence of antiretroviral resistance [ Time Frame: From date of transplant through end of follow-up, up to 4 years ]
    Measured by local sites' Clinical Laboratory Improvement Amendments (CLIA) certified lab with episode of HIV breakthrough defined as 2 consecutive plasma HIV viral loads >200 copies/mL or one HIV viral load >1000 copies/mL after a period of virologic control post-transplant

  29. Incidence of X4 tropic virus [ Time Frame: From date of transplant through end of follow-up, up to 4 years ]
    Measured by local sites' Clinical Laboratory Improvement Amendments (CLIA) certified lab with episode of HIV breakthrough defined as 2 consecutive plasma HIV viral loads >200 copies/mL or one HIV viral load >1000 copies/mL after a period of virologic control post-transplant

  30. Incidence of opportunistic infection [ Time Frame: From date of transplant through end of follow-up, up to 4 years ]
    Cumulative incidence of opportunistic infections

  31. Incidence of surgical complications [ Time Frame: From date of transplant through year 1 ]
    Number of surgical complications within 1 year of transplant, e.g. delayed closure, wound dehiscence

  32. Incidence of vascular complications [ Time Frame: From date of transplant through year 1 ]
    Number of vascular complications within 1 year of transplant

  33. Incidence of viral-related malignancies [ Time Frame: From date of transplant through end of follow-up, up to 4 years ]
    Number of malignancies as determined by local pathology

  34. Incidence of the formation of de novo donor-specific human leukocyte antigen(HLA) antibodies [ Time Frame: From date of transplant through end of year 1 ]
    Proportion of participants with a de novo donor-specific HLA antibody as measured and reported by local sites' lab

  35. Composite event, time to first [ Time Frame: From date of transplant through end of follow-up, up to 4 years ]
    Time to first of any of these events: all-cause-mortality or graft failure or renal allograft rejection or HIV breakthrough or HIV virologic failure or AIDS defining illness



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Participant meets the standard criteria for kidney transplant at the local center.
  • Participant is able to understand and provide informed consent.
  • Participant meets with an independent advocate per the HIV Organ Policy Equity (HOPE) Act Safeguards.
  • Documented HIV infection (by any licensed assay, or documented history of detectable HIV-1 RNA).
  • No living donor available.
  • Participant is ≥18 years old.
  • Opportunistic complications: if prior history of an opportunistic infection, the participant has received appropriate therapy and has no evidence of active disease.
  • Cluster of Differentiation 4 (CD4)+ T-cell: ≥200/µL within 16 weeks of transplant.
  • HIV-1 is below 50 copies RNA/mL. Viral blips between 50-400 copies allowed as long as there are not consecutive measurements >200 copies/mL.
  • Participant is willing to comply with all medication related to their transplant and HIV management.
  • For participant with a history of aspergillus colonization or disease, no evidence of active disease.
  • The participant must have, or be willing to start seeing, a primary medical care provider with expertise in HIV management.
  • All participants participating in sexual activity that could lead to pregnancy must use an FDA approved method of birth control.
  • Participant is not suffering from significant wasting (e.g. body mass index <21) thought to be related to HIV disease.

Exclusion Criteria:

  • Participant has a history of progressive multifocal leukoencephalopathy (PML) or primary central nervous system (CNS) lymphoma.
  • Participant is pregnant or breastfeeding.
  • Past or current medical problems or findings from medical history, physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks or may impact the quality or interpretation of the data obtained from the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03500315


Contacts
Contact: Christine Durand, MD 410-955-5684 cdurand2@jhmi.edu
Contact: Dorry Segev, MD, PhD 410-502-6115 dorry@jhmi.edu

  Show 23 Study Locations
Sponsors and Collaborators
Johns Hopkins University
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Christine Durand, MD Johns Hopkins University

Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03500315     History of Changes
Other Study ID Numbers: IRB00141138
U01AI134591 ( U.S. NIH Grant/Contract )
First Posted: April 17, 2018    Key Record Dates
Last Update Posted: September 24, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No