Renal Transplantation and Raltegravir in HIV-Infected Patients

HIV-1 Infection Clinical Trial

— ANRS153TREVE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01453192
• Other study ID #: 2011-001004-35
• Secondary ID: ANRS 153 TREVE
• Status: Completed
• Phase: Phase 3
• First received: October 3, 2011
• Last updated: July 11, 2016
• Start date: December 2011
• Est. completion date: November 2015

Study information

• Verified date: July 2016
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Renal Insufficiency
• HIV-1 Infection
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• Raltegravir
Introduction of Raltegravir 2 days after renal transplantation within an antiretroviral regimen without ritonavir boosted antiprotease

Locations

Country	Name	City	State
France	Hôpital Pellegrin, Service de Nephrologie, Transplantation Rénale, Dialyse	Bordeaux
France	CHU De Caen, Service de Néphrologie Hémodialyse	Caen
France	Hôpital Henri Mondor, Service de Néphrologie Transplantation	Créteil
France	Hôpital Kremlin Bicêtre, Service de Néphrologie	Kremlin Bicêtre
France	CHRU Lille, Service de néphrologie	Lille
France	CHU de Nantes, Service de Néphrologie et Immunologie Clinique	Nantes
France	Hôpital Pasteur, Service de Néphrologie - Transplantation	Nice
France	Hôpital Necker, Service de Néphrologie adulte	Paris
France	Hopital Saint Louis, Service de Néphrologie	Paris
France	Hôpital TENON, Urgences Néphrologiques et Transplantation Rénale	Paris
France	Hôpital civil, Service de Néphrologie et Transplantation	Strasbourg
France	Hôpital Foch, Service de Néphrologie Transplantation	Suresnes
France	Hôpital Rangueil, Service de Néphrologie, HTA, Dialyse, Transplantation	Toulouse
France	Hôpital Bretonneau, Service de Néphrologie	Tours

Sponsors (2)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of acute clinical renal graft rejection	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	6 months	Yes
Secondary	Incidence of acute clinical and subclinical renal graft rejection	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.	1 year	Yes
Secondary	One year graft survival	One year graft survival, compared to non HIV-infected transplanted patients, using data provided by French Biomedicines Agency	1 year	Yes
Secondary	Patients' survival	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	1 year	Yes
Secondary	Phenotyping of lymphocytic infiltrates in case of acute rejection	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.	1 year	Yes
Secondary	Incidence of AIDS defined diseases and severe morbidity diseases after renal transplantation	Severe morbidity diseases include: pathological infections, malignancies, metabolic and cardiovascular diseases.	1 year	Yes
Secondary	Immunological and virologic status after renal transplantation	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.	1 year	Yes
Secondary	Evaluation of the switch by raltegravir at the time of renal transplantation	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.	1 year	Yes
Secondary	Viral load control after switch by antiretroviral treatment including raltegravir after renal transplantation	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.	1 year	Yes
Secondary	Survival and waiting period of HIV patients registered on French biomedicine agency for renal transplantation	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 )	1 year	Yes
Secondary	Measurement of Area under plasma concentration (AUC) variability of immunosuppressive drugs after introduction of antiretroviral regimen containing Raltegravir	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.	1 year	Yes

External Links

•   French National Agency for Research on AIDS and viral Hepatitis