Transplantation and the Use of Raltegravir in HIV-Infected Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Duke University
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01793467
First received: February 13, 2013
Last updated: February 19, 2013
Last verified: February 2013
  Purpose

Raltegravir (RAL) is a preferred option for initial antiretroviral therapy in the most recent HIV Treatment Guidelines and is emerging as a popular choice for use in the specialized population of HIV-infected patients being considered for solid organ transplantation. Data from HIV-infected persons with normal organ function have revealed few raltegravir-associated metabolic complications compared to older antiretrovirals, and in general, drug-drug interactions with raltegravir are infrequent. The absence of such concerns appears to make raltegravir a potentially appealing option for antiretroviral therapy in HIV-infected patients being considered for solid organ transplantation.

At present, however, little is known of the safety and long term tolerability of RAL-containing regimens in persons undergoing solid organ transplantation. As more HIV-infected patients undergo organ transplantation, there is a growing need for good data on such things as the effect of dialysis on RAL concentrations, the potential interactions with commonly used immunosuppressive drugs, and the pharmacokinetic (PK) /pharmacodynamic (PD) characteristics in those with end stage organ failure, as well as those with functioning grafts.

The proposed study will also examine transplant function and survival in HIV-infected patients receiving RAL-containing ART and will compare it to HIV negative historic controls.


Condition
HIV Positive
Organ Transplant Recipient
Active Wait Listing for Organ Transplant

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Solid Organ Transplantation and the Use of Raltegravir in HIV-Infected Patients: An Observational Study of Pharmacokinetics, Safety, Tolerability and Efficacy

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • To examine raltegravir (RAL) in the management of HIV-infected persons listed for solid organ transplantation, with a focus on mortality and graft survival [ Time Frame: 3+ years ]

Secondary Outcome Measures:
  • Assess Raltegravir viability as a long term HIV treatment drug for patients undergoing transplant [ Time Frame: 3+ years ]
    1. Characterize the effect of raltegravir-based regimens on the pre and post-transplant endocrine and cardiovascular effects
    2. Evaluate drug-drug interactions between raltegravir and current transplant immunosuppressant regimens.
    3. Determine RAL pharmacokinetic (PK) profile in HIV-infected patients with end organ failure before and after organ transplantation.

    a) Measure RAL PK in HIV-infected patients with end-stage renal failure (ESRF), who are receiving dialysis pre-transplant.

    b) Assess raltegravir PK in patients with different severities of liver disease, including cirrhosis, when such patients are available.

    d) Assess the ability of RAL-centered ART combinations to maintain HIV suppression and CD4 counts following solid-organ transplant.


  • determine the viability of grafted organs in patients with HIV infections [ Time Frame: 3+ years ]
    1. Track adverse events including those attributable to ART therapy, but also routine post-transplant events. Assess the safety and tolerability profile of RAL during the pre and post-transplant period.
    2. Determine graft survival and performance following transplantation in this population and compare to similar data in HIV-negative historical controls.


Study Start Date: October 2012
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Detailed Description:

Pre-transplant:

  • Patients on stable antiretroviral regimens who undergo evaluation for transplantation and are subsequently placed on the transplant waiting list will be considered for inclusion in the study. The details of the cART for each patient will remain the sole purview of the patient and the patient's HIV care provider.
  • To be considered for solid organ transplantation, in addition to routine transplant listing criteria, the patient must fulfill the following criteria:
  • 1. non-pregnant adult patient with CD4 count >200/μL;
  • 2. no concurrent active AIDS-defining infections or malignancy;
  • 3. at least 24 months of well controlled HIV viremia, defined as <50 copies for the majority of the time.

After all screening procedures have been completed to ensure eligibility, a pre-transplant pharmacokinetic study will be done as described below. Using specimens obtained during 7 time points, patient-specific Cmax, Cmin and AUC determinations will be made using standard calculation approaches. The PK data will also include samples drawn on dialysis days for patients with End-stage renal failure:- pre-dialysis, arterial and venous concentrations (Cin and Cout) at the beginning of dialysis, and post dialysis levels (to determine individual hemodialysis extraction ratios).

Additional data to be collected include a Quality of Life questionnaire, SF-36, and a PHQ-9 depression screen which will be administered as a baseline test done at enrollment. Patients will be asked to have a dual-emission X-ray absorptiometry (DEXA) scan prior to transplant (unless this has been completed within two years of enrollment).

Peri-transplant Assessments:

In addition to the standard of care laboratory and imaging procedures that are done around the time of organ transplantation, the following research samples will be collected:

  • Pre-transplant - RAL concentrations
  • In addition, the following information will be recorded from the subject's medical record: full HIV and infective history and test results including CD4 count, and percentage, HIV viral load, electrocardiography (to assess QTc interval), CMV-IgG/IgM, Hepatitis B, C, D screens +/- viral loads if not already determined.

Post-transplant inpatient hospitalization

  • RAL concentrations as well as HIV viral load and CD4/CD8 lymphocyte populations.
  • In addition, the following information will be recorded from the subject's medical record: test results including EKG (to assess QTc interval).

Post-transplant:

  • RAL concentrations will be collected at Months 1 and 3 only.
  • In addition to the routine post-transplant care, the following information will be collected from the subject's medical records at study months 1, 3, 6, 9, 12, 24 post transplant: CD4 count and %, HIV viral load (+/- genotype and integrase mutation analysis if viral rebound occurs), Vitamin D, Basic Metabolic Panel (to calculate ClCr), quantitative urinary creatinine and protein excretion. Patient side-effect card will be ascertained by directed questioning from the study coordinator at each visit.

Repeat DEXA scan will be done at the 24 months post-transplant visit. Quality of Life assessment and depression screening tools will be administered at the 6 and 24 month marks.

  Eligibility

Ages Eligible for Study:   13 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

HIV positive patients, awaiting or listed for organ transplantation, currently taking Raltegravir

Criteria

Inclusion Criteria:

  • 1. non-pregnant adult patient with CD4 count >200/μL
  • 2. no concurrent active AIDS-defining infections or malignancy
  • 3. at least 24 months of well controlled HIV viremia, defined as <50 copies for the majority of the time.
  • 4. otherwise suitable transplant candidates, actively listed
  • 5. currently taking Raltegravir for control of HIV infection
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01793467

Contacts
Contact: Cameron R Wolfe, MD 9196680789 cameron.wolfe@duke.edu
Contact: Charles B Hicks, MD 9196848111

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 277138270
Contact: Cameron R Wolfe, MD    919-668-0789    cameron.wolfe@duke.edu   
Principal Investigator: Cameron R Wolfe, MD         
Sponsors and Collaborators
Duke University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Cameron R Wolfe, MD Duke University
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01793467     History of Changes
Other Study ID Numbers: Pro00036598
Study First Received: February 13, 2013
Last Updated: February 19, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
HIV Seropositivity
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on July 23, 2014