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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
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)
ClinicalTrials.gov Identifier:
NCT01453192
First received: October 3, 2011
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
HIV-1 Infection
Chronic Renal Insufficiency
Drug: Raltegravir
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Incidence of acute clinical renal graft rejection [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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:
  • Incidence of acute clinical and subclinical renal graft rejection [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.

  • One year graft survival [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    One year graft survival, compared to non HIV-infected transplanted patients, using data provided by French Biomedicines Agency

  • Patients' survival [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

    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


  • Phenotyping of lymphocytic infiltrates in case of acute rejection [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of AIDS defined diseases and severe morbidity diseases after renal transplantation [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Severe morbidity diseases include: pathological infections, malignancies, metabolic and cardiovascular diseases.

  • Immunological and virologic status after renal transplantation [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.

  • Evaluation of the switch by raltegravir at the time of renal transplantation [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.

  • Viral load control after switch by antiretroviral treatment including raltegravir after renal transplantation [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.

  • Survival and waiting period of HIV patients registered on French biomedicine agency for renal transplantation [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 )

  • Measurement of Area under plasma concentration (AUC) variability of immunosuppressive drugs after introduction of antiretroviral regimen containing Raltegravir [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 50
Study Start Date: December 2011
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
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: NCT01453192

Contacts
Contact: Philippe GRIMBERT, MD +33 149814451 philippe.grimbert@hmn.aphp.fr
Contact: Marie MATIGNON, MD +33 149814451 marie.matignon@hmn.aphp.fr

Locations
France
Hôpital Pellegrin, Service de Nephrologie, Transplantation Rénale, Dialyse Not yet recruiting
Bordeaux, France, 33076
Contact: Pierre MERVILLE         
Principal Investigator: Pierre MERVILLE         
CHU De Caen, Service de Néphrologie Hémodialyse Recruiting
Caen, France, 14033
Contact: Bruno HURAULT DE LIGNY         
Principal Investigator: Bruneau HURAULT DE LIGNY         
Hôpital Henri Mondor, Service de Néphrologie Transplantation Recruiting
Créteil, France, 94010
Contact: Philippe Grimbert, Pr         
Principal Investigator: Philippe Grimbert         
Hôpital Kremlin Bicêtre, Service de Néphrologie Recruiting
Kremlin Bicêtre, France, 94275
Contact: Antoine DURRBACH, MD         
Principal Investigator: Antoine DURRBACH, MD         
CHRU Lille, Service de néphrologie Not yet recruiting
Lille, France, 59037
Contact: Marc HAZZAN         
Principal Investigator: Marc HAZZAN         
CHU de Nantes, Service de Néphrologie et Immunologie Clinique Not yet recruiting
Nantes, France, 44093
Contact: Jacques DANTAL         
Principal Investigator: Jacques DANTAL         
Hôpital Pasteur, Service de Néphrologie - Transplantation Not yet recruiting
Nice, France, 06002
Contact: Elisabeth CASSUTO         
Principal Investigator: Elisabeth CASSUTO         
Hôpital TENON, Urgences Néphrologiques et Transplantation Rénale Not yet recruiting
Paris, France, 75970
Contact: Eric RONDEAU         
Principal Investigator: Eric RONDEAU         
Hopital Saint Louis, Service de Néphrologie Not yet recruiting
Paris, France, 75010
Contact: Marie-Noëlle PERALDI         
Principal Investigator: Marie-Noëlle PERALDI         
Hôpital Necker, Service de Néphrologie adulte Not yet recruiting
Paris, France, 75743
Contact: Christophe LEGENDRE         
Principal Investigator: Christophe LEGENDRE         
Hôpital civil, Service de Néphrologie et Transplantation Not yet recruiting
Strasbourg, France, 67091
Contact: Bruno MOULIN         
Principal Investigator: Bruno MOULIN         
Hôpital Foch, Service de Néphrologie Transplantation Not yet recruiting
Suresnes, France, 92151
Contact: Leila TRICOT         
Principal Investigator: Leila TRICOT         
Hôpital Rangueil, Service de Néphrologie, HTA, Dialyse, Transplantation Not yet recruiting
Toulouse, France, 31059
Contact: Lionel ROSTAING         
Principal Investigator: Lionel ROSTAING         
Hôpital Bretonneau, Service de Néphrologie Not yet recruiting
Tours, France, 37044
Contact: Yvon LEBRANCHU         
Principal Investigator: Yvon LEBRANCHU         
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

Additional Information:
No publications provided

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
Study First Received: October 3, 2011
Last Updated: July 30, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on October 19, 2014