Clinical trial NCT03734393: HOPE in Action Trial of HIV+ Deceased Donor Liver Transplants for HIV+ Recipients
Official title: HOPE in Action Prospective Multicenter, Clinical Trial of HIV+ Deceased Donor Liver Transplants for HIV+ Recipients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hiv
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2018-11-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: This study will evaluate if receiving a liver transplant from an HIV-infected deceased liver donor is safe with regards to survival and major transplant-related and HIV-related complications compared to receiving a liver from an HIV-uninfected deceased liver 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

Eligibility criteria: Inclusion Criteria:

* Participant meets the standard criteria for liver transplant at the local center.
* Participants being listed for a simultaneous liver kidney (SLK) are eligible if participants meet the standard criteria for both organs.
* Participant is able to understand and provide informed consent.
* Participant meets with an independent advocate per the HIV Organ Policy Equity (HOPE) Act Safeguards and Research Criteria.
* Documented HIV infection (by any licensed assay or documented history of detectable HIV-1 RNA).\*
* Participant is ≥ 18 years old.
* Opportunistic complications: prior history of certain opportunistic infections is not an exclusion if the participant has received appropriate therapy and has no evidence of active disease. Medical record documentation should be provided whenever possible.
* CD4+ T-cell count: ≥ 100/µL within 16 weeks prior to transplant if no history of AIDS-defining infection; or ≥ 200 μL if history of opportunistic infection is present.
* HIV-1 RNA is below 50 RNA/mL.\* Viral blips between 50-400 copies will be allowed as long as there are not consecutive measurements \> 200 copies/mL. \*Organ recipients who are unable to tolerate anti-retroviral therapy (ART) due to organ.

failure or recently started ART may be eligible despite a detectable viral load if safe and effective ART to be used by the recipient after transplantation is described.

* Participant must have or be willing to start seeing a primary medical care provider with expertise in HIV management.
* Participant is willing to comply with all medications related to participant's transplant and HIV management.
* For participants with a history of aspergillus colonization or disease, no current clinical evidence of active disease.
* Agreement to use contraception.
* 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. (Note: Participants who become pregnant post-transplant will continue to be followed in the study and will be managed per local site practice. Women that become pregnant should not breastfeed.)
* 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 from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Primary outcomes:
measure: Time to first death or graft failure or serious adverse event (SAE) or HIV breakthrough or opportunistic infection as a composite measure
timeFrame: From date of transplant through administrative censorship at study completion, up to 4 years
Secondary outcomes:
measure: Time to Pre-transplant mortality
timeFrame: From date of enrollment to date of transplant or death of any cause, whichever comes first, assessed up to 4 years
measure: Graft Failure as assessed by Time to first occurrence of mortality or re-transplant or return to maintenance dialysis
timeFrame: From date of transplant through administrative censorship at study completion, up to 4 years
measure: 1-year acute liver rejection
timeFrame: From date of transplant to end of year 1
measure: 2-year acute liver rejection
timeFrame: From date of transplant to end of year 2
measure: 3-year acute liver rejection
timeFrame: From date of transplant to end of year 3
measure: Number of graft rejections in liver transplant
timeFrame: From date of transplant to end of year 3
measure: 6-month acute kidney rejection in simultaneous liver/kidney transplant recipients
timeFrame: From date of transplant to 6 months post transplant
measure: 1-year acute kidney rejection in simultaneous liver/kidney transplant recipients only
timeFrame: From date of transplant to end of year 1
measure: Number of Non-alcoholic fatty liver (NAFL)
timeFrame: From date of transplant through end of follow-up, up to 3 years
measure: Number of steatohepatitis (NASH)
timeFrame: From date of transplant through end of follow-up, up to 3 years
measure: Trajectory of recipient Cluster of Differentiation (CD4) count over time
timeFrame: From date of transplant through end of follow up, up to 4 years
measure: Trajectory of recipient plasma HIV RNA over time
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Graft function as assessed by Fibrosis-4 index
timeFrame: 1 years post-transplant
measure: Graft function as assessed by Fibrosis-4 index
timeFrame: 2 years post-transplant
measure: Graft function as assessed by Fibrosis-4 index
timeFrame: 3 years post-transplant
measure: Graft function as assessed by Fibrosis-4 index
timeFrame: 4 years post-transplant
measure: Graft function as assessed by incidence of fibrosis
timeFrame: From date of transplant through end of follow-up, up to 3 years
measure: Graft function as assessed by liver stiffness
timeFrame: 1 year post-transplant
measure: Graft function as assessed by liver stiffness
timeFrame: 2 years post-transplant
measure: Graft function as assessed by liver stiffness
timeFrame: 3 years post-transplant
measure: Average graft function as assessed by aspartate aminotransferase (AST)
timeFrame: 1 year post-transplant
measure: Average graft function as assessed by AST
timeFrame: 2 years post-transplant
measure: Average graft function as assessed by AST
timeFrame: 3 years post-transplant
measure: Average graft function as assessed by AST
timeFrame: 4 years post-transplant
measure: Average graft function as assessed by alanine aminotransferase (ALT)
timeFrame: 1 year post-transplant
measure: Average graft function as assessed by ALT
timeFrame: 2 years post-transplant
measure: Average Graft function as assessed by ALT
timeFrame: 3 years post-transplant
measure: Average graft function as assessed by ALT
timeFrame: 4 years post-transplant
measure: Average graft function as assessed by bilirubin
timeFrame: 1 year post-transplant
measure: Average graft function as assessed by bilirubin
timeFrame: 2 years post-transplant
measure: Average graft function as assessed by bilirubin
timeFrame: 3 years post-transplant
measure: Average graft function as assessed by Bilirubin
timeFrame: 4 years post-transplant
measure: Graft function as assessed by Mean calculated Model for End Stage Liver Disease (MELD) score
timeFrame: 1 year post-transplant
measure: Graft function as assessed by Mean calculated MELD score
timeFrame: 2 years post-transplant
measure: Graft function as assessed by Mean calculated MELD score
timeFrame: 3 years post-transplant
measure: Graft function as assessed by Mean calculated MELD score
timeFrame: 4 years post-transplant
measure: Graft function as assessed by AST to Platelet Ratio (APRI) index
timeFrame: 1 year post-transplant
measure: Graft function as assessed by AST to Platelet Ratio (APRI) index
timeFrame: 2 years post-transplant
measure: Graft function as assessed by AST to Platelet Ratio (APRI) index
timeFrame: 3 years post-transplant
measure: Graft function as assessed by AST to Platelet Ratio (APRI) index
timeFrame: 4 years post-transplant
measure: Metabolic Outcome as assessed by Body mass index (BMI)
timeFrame: 1 year post-transplant
measure: Metabolic Outcome as assessed by Body mass index (BMI)
timeFrame: 2 years post-transplant
measure: Metabolic Outcome as assessed by Body mass index (BMI)
timeFrame: 3 years post-transplant
measure: Metabolic Outcome as assessed by Body mass index (BMI)
timeFrame: 4 years post-transplant
measure: Average hemoglobin a1c among participants at 1 year
timeFrame: 1 years post-transplant
measure: Average hemoglobin a1c among participants at 2 years
timeFrame: 2 years post-transplant
measure: Average hemoglobin a1c among participants at 3 years
timeFrame: 3 years post-transplant
measure: Average hemoglobin a1c among participants at 4 years
timeFrame: 4 years post-transplant
measure: Number of HIV breakthroughs
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Number of opportunistic infections
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Number of X4 tropic virus breakthroughs
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Number of vascular complications
timeFrame: From date of transplant through year 1
measure: Number of surgical complications
timeFrame: From date of transplant through year 1
measure: Number of viral-related malignancies
timeFrame: From date of transplant through end of follow-up, up to 4 years
measure: Hepatitis C (HCV) sustained viral response post-transplant
timeFrame: 12 weeks HCV treatment
measure: Number of the formation of de novo donor-specific human leukocyte antigen(HLA) antibodies
timeFrame: From date of transplant through end of year 1
measure: Time to first occurrence of all-cause-mortality or graft failure or renal allograft rejection or HIV breakthrough or HIV virologic failure or AIDS defining illness as a composite measure
timeFrame: From date of transplant through end of follow-up, up to 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown Transplant Institute
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland, Institute of Human Virology
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC - University of Pittsburgh Medical Center
state: Pennsylvania
city: Memphis
country: United States
facility: University of Tennessee Health and Science Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: Johns Hopkins University
name: Christine Durand, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Werbel WA, Brown DM, Kusemiju OT, Doby BL, Seaman SM, Redd AD, Eby Y, Fernandez RE, Desai NM, Miller J, Bismut GA, Kirby CS, Schmidt HA, Clarke WA, Seisa M, Petropoulos CJ, Quinn TC, Florman SS, Huprikar S, Rana MM, Friedman-Moraco RJ, Mehta AK, Stock PG, Price JC, Stosor V, Mehta SG, Gilbert AJ, Elias N, Morris MI, Mehta SA, Small CB, Haidar G, Malinis M, Husson JS, Pereira MR, Gupta G, Hand J, Kirchner VA, Agarwal A, Aslam S, Blumberg EA, Wolfe CR, Myer K, Wood RP, Neidlinger N, Strell S, Shuck M, Wilkins H, Wadsworth M, Motter JD, Odim J, Segev DL, Durand CM, Tobian AAR; HOPE in Action Investigators. National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States. Clin Infect Dis. 2022 Jun 10;74(11):2010-2019. doi: 10.1093/cid/ciab743.