Renal Transplantation and Raltegravir in HIV-Infected Patients (ANRS153 TREVE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 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 11, 2013
Last verified: July 2013

October 3, 2011
July 11, 2013
November 2011
November 2014   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01453192 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Renal Transplantation and Raltegravir in HIV-Infected Patients
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

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.

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.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV-1 Infection
  • Chronic Renal Insufficiency
Drug: Raltegravir
Introduction of Raltegravir 2 days after renal transplantation within an antiretroviral regimen without ritonavir boosted antiprotease
Other Name: Isentress
Experimental: Raltegravir
Raltegravir associated to an antiretroviral regimen without ritonavir boosted antiprotease
Intervention: Drug: Raltegravir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
November 2015
November 2014   (final data collection date for primary outcome measure)

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)
Both
18 Years to 70 Years
No
Contact: Philippe GRIMBERT, MD +33 149814451 philippe.grimbert@hmn.aphp.fr
Contact: Marie MATIGNON, MD +33 149814451 marie.matignon@hmn.aphp.fr
France
 
NCT01453192
2011-001004-35, ANRS 153 TREVE
Yes
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Merck Sharp & Dohme Corp.
Principal Investigator: Philippe GRIMBERT, MD CHU Henri-Mondor
Study Director: Dominique COSTAGLIOLA, PHD INSERM U943
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP