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Renal Transplantation and Raltegravir in HIV-Infected Patients (ANRS153TREVE)

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ClinicalTrials.gov Identifier: NCT01453192
Recruitment Status : Completed
First Posted : October 17, 2011
Last Update Posted : July 12, 2016
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Study Description
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Brief Summary:
The aim of this study is to evaluate the incidence of acute renal graft rejection 6 months after transplantation in HIV-infected patients under three antiretroviral drugs regimen including Raltegravir.

Condition or disease Intervention/treatment Phase
HIV-1 Infection Chronic Renal Insufficiency Drug: Raltegravir Phase 3

Detailed Description:

Antiretroviral treatment of HIV-1 Infection might interact with immunosuppressive treatments which increase rejection of renal graft incidence.

In addition HIV infection may be modified together with cardiovascular risk. Patients participating to this study will receive after transplantation antiretroviral regimen including Raltegravir.

Raltegravir treatment does not interact with immunosuppressive drugs and thus seems to be the treatment of choice to be associated with immunosuppressive drugs.


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: National, Multicenter, Phase III Prospective Trial About Clinical and Immunological Follow-up After Renal Transplantation in HIV-1 Infected Patients With End Stage Chronic Renal Insufficiency
Study Start Date : December 2011
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015

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U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Raltegravir
Raltegravir associated to an antiretroviral regimen without ritonavir boosted antiprotease
 Drug: Raltegravir
Introduction of Raltegravir 2 days after renal transplantation within an antiretroviral regimen without ritonavir boosted antiprotease
Other Name: Isentress


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of acute clinical renal graft rejection [ Time Frame: 6 months ]
    Incidence of acute clinical renal graft rejection defined by 20% increase of serum creatinine, associated to histological features (Banff classification) 6 months after renal transplantation


Secondary Outcome Measures :
  1. Incidence of acute clinical and subclinical renal graft rejection [ Time Frame: 1 year ]
    Incidence of acute clinical and subclinical renal graft rejection up to 1 year after renal transplantation defined only by renal histology (without creatinine modification). Histology is performed on routine renal graft biopsy 3 months and 1 year after transplantation.

  2. One year graft survival [ Time Frame: 1 year ]
    One year graft survival, compared to non HIV-infected transplanted patients, using data provided by French Biomedicines Agency

  3. Patients' survival [ Time Frame: 1 year ]

    Patients survival, compared to:

    - chronic dialysis HIV patients still listed on the transplantation waiting list - transplanted non-HIV patients using data provide by French Biomedicine Agency


  4. Phenotyping of lymphocytic infiltrates in case of acute rejection [ Time Frame: 1 year ]
    The aim of the immunological phenotyping is to analyse the expression of activation markers between different TCD4 and TCD8 sub-population, this phenotyping will be compared to those observed in acute cell-mediated rejection occurring in the historical cohort of Non-HIV patients. In addition, the rate and expression of Treg population will be evaluated.

  5. Incidence of AIDS defined diseases and severe morbidity diseases after renal transplantation [ Time Frame: 1 year ]
    Severe morbidity diseases include: pathological infections, malignancies, metabolic and cardiovascular diseases.

  6. Immunological and virologic status after renal transplantation [ Time Frame: 1 year ]
    Immunological (lymphocyte activation and inflammatory parameters) and virologic status (kinetics of viral replication: HIV RNA in blood, total HIV DNA in PBMC) monitoring after renal transplantation. These parameters will be compared with pre-transplant status.

  7. Evaluation of the switch by raltegravir at the time of renal transplantation [ Time Frame: 1 year ]
    Assessment of ARV medications change and introduction of raltegravir at the time of renal transplantation in terms of reduction of pharmacokinetic interaction between antiretroviral regimen including raltegravir and immunosupressive treatments. In addition, virological efficacy of antiretroviral treatment including Raltegravir will be evaluated.

  8. Viral load control after switch by antiretroviral treatment including raltegravir after renal transplantation [ Time Frame: 1 year ]
    The aim of this study is to evaluate at the time of renal transplantation the virologic efficiency after the switch by an antiretroviral regimen including Raltegravir in terms of viral load control an virological failure as Raltegravir is known for its low genetic barrier.

  9. Survival and waiting period of HIV patients registered on French biomedicine agency for renal transplantation [ Time Frame: 1 year ]
    Assessment of HIV patients' waiting period until renal transplantation and survival of patients registered on French biomedicine agency waiting-list compared to Non-HIV population (data provided by French Biomedicine Agency )

  10. Measurement of Area under plasma concentration (AUC) variability of immunosuppressive drugs after introduction of antiretroviral regimen containing Raltegravir [ Time Frame: 1 year ]
    Area under plasma concentration (AUC) of Raltegravir and immunosuppressive drugs (Tacrolimus and Mycophenolate Mophetyl) will be measured as well as residual concentration of Tacrolimus. This study is performed in order to verify immunosupressive treatments dosage adaptation.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Registration on the French national renal transplantation waiting list (Biomedicines Agency) for a living or cadaveric donor organ
  • HIV-1-infected patients treated by a three-drug ARV regimen
  • Immuno-virologic criteria at renal transplantation: undetectable viral load (<50 copies/mL) and CD4 >200/mm3 for at least three months on stable ARV
  • Age >18 years and <70 years
  • Effective contraception for women
  • Written informed consent
  • Patient with social security coverage

Exclusion Criteria:

  • Permanent:

    • Hepatic cirrhosis
    • Serious psychiatric illness history
    • EBV or HHV8 lymphoproliferation (lymphoma, systemic Kaposi's sarcoma or multifocal Castleman's disease)
    • History of PML
    • HTLV-1 seropositivity
    • Severe pulmonary or cardiovascular disease with poor short-term vital prognosis
    • Patient with AgHBs+
    • History of cryptosporidiosis
    • History of fungal infection with multi resistant fungi not likely to respond to oral antifungal therapy
    • Impossibility or refusal of Raltegravir switch, decision made by doctor or patient

  • Temporary:

    • Recent malignancy (between 2 and 5 years according to type)
    • HPV-related cervical or anal disease: carcinoma in situ, AIN III, CIN III in remission for less than three years
    • Active infection
    • HCV infection (PCR-positive)
Contacts and Locations
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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): NCT01453192


Locations
France
Hôpital Pellegrin, Service de Nephrologie, Transplantation Rénale, Dialyse
Bordeaux, France, 33076
CHU De Caen, Service de Néphrologie Hémodialyse
Caen, France, 14033
Hôpital Henri Mondor, Service de Néphrologie Transplantation
Créteil, France, 94010
Hôpital Kremlin Bicêtre, Service de Néphrologie
Kremlin Bicêtre, France, 94275
CHRU Lille, Service de néphrologie
Lille, France, 59037
CHU de Nantes, Service de Néphrologie et Immunologie Clinique
Nantes, France, 44093
Hôpital Pasteur, Service de Néphrologie - Transplantation
Nice, France, 06002
Hopital Saint Louis, Service de Néphrologie
Paris, France, 75010
Hôpital Necker, Service de Néphrologie adulte
Paris, France, 75743
Hôpital TENON, Urgences Néphrologiques et Transplantation Rénale
Paris, France, 75970
Hôpital civil, Service de Néphrologie et Transplantation
Strasbourg, France, 67091
Hôpital Foch, Service de Néphrologie Transplantation
Suresnes, France, 92151
Hôpital Rangueil, Service de Néphrologie, HTA, Dialyse, Transplantation
Toulouse, France, 31059
Hôpital Bretonneau, Service de Néphrologie
Tours, France, 37044
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Philippe GRIMBERT, MD CHU Henri-Mondor
Study Director: Dominique COSTAGLIOLA, PHD INSERM U943
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:
French National Agency for Research on AIDS and viral Hepatitis  This link exits the ClinicalTrials.gov site

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT01453192     History of Changes
Other Study ID Numbers: 2011-001004-35
ANRS 153 TREVE ( Registry Identifier: ANRS )
First Posted: October 17, 2011    Key Record Dates
Last Update Posted: July 12, 2016
Last Verified: July 2016

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
Raltegravir
Renal transplantation
HIV-1
Acute renal graft rejection

Additional relevant MeSH terms:
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
 Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action