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Clinical Trials

MainTitle

Efficacy and Safety of 2 Raltegravir Doses in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis

This study has been completed
Sponsor
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Collaborator
Gilead Sciences
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
NCT00822315

First received: January 13, 2009
Last updated: July 16, 2013
Last Verified: July 2013
History of Changes
Purpose

Purpose

Raltegravir is a potent antiretroviral agent that could be used as an alternative to efavirenz in HIV-1 infected patients with tuberculosis. However due to pharmacokinetic interactions, the optimal dose of raltegravir to be used in combination with rifampin is currently unknown.

This phase II open-label randomized multicenter trial is designed to estimate the antiviral efficacy of two doses of raltegravir and one dose of efavirenz at week 24, in HIV-1 naive patients co-infected with active tuberculosis (TB) treated with rifampin.

Condition Intervention Phase
HIV Infections
Tuberculosis

Drug : efavirenz
Drug : raltegravir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Open-label Randomized Multicenter Trial to Compare the Efficacy and Safety of Two Different Doses of Raltegravir and Efavirenz, All in Combination With Tenofovir and Lamivudine, in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis

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

  • Virologic success, using Time to Loss of Virologic Response (TLOVR) algorithm: -Plasma HIV RNA below 50 copies/ml at week 20, confirmed at week 24 -Absence of permanent treatment discontinuation -Absence of death -Still follow-up at week 24 [ Time Frame: 24 weeks ]
Secondary Outcome Measures:
  • Proportion of patients with virologic response with the following definitions: - Plasma HIV RNA <50 copies/ml at week 24 - Rate of strategy discontinuation and treatment changes - Proportion of death - Proportion of patients loss to follow-up [ Time Frame: 24 weeks ]
  • Proportion of patients with virologic response with the following definitions: o Plasma HIV RNA <50 copies/ml o Plasma HIV RNA <400 copies/ml [ Time Frame: 24 and 48 weeks ]
  • Evolution in HIV RNA and HIV DNA (total and 2 LTR circular) from baseline to week 48 [ Time Frame: 48 weeks ]
  • Rate of viral resistance mutations in the plasma at the time of virologic failure and in comparison with HIV-RNA mutations at W0 [ Time Frame: At the time of virologic failure ]
  • Evolution of CD4 cell counts from baseline to week 48 [ Time Frame: 48 weeks ]
  • Frequency, type and time to a new AIDS-defining event or death [ Time Frame: Through out the trial ]
  • Frequency, type, time to grade 3 or 4 adverse event [ Time Frame: Through out the trial ]
  • Rate of success of TB treatment [ Time Frame: 48 weeks ]
  • Anti-TB resistance rate [ Time Frame: 48 weeks ]
  • Evolution of raltegravir and efavirenz trough concentration [ Time Frame: Through out the trial ]

Enrollment: 155
Study Start Date: July 2009
Study Completion Date: May 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: 1
efavirenz
Drug: efavirenz

tenofovir 245 mg / lamivudine 300 mg / efavirenz 600 mg

Experimental: 2
raltegravir 400 mg
Drug: raltegravir

tenofovir 245 mg / lamivudine 300 mg / raltegravir 400 mg

Experimental: 3
raltegravir 800 mg
Drug: raltegravir

tenofovir 245 mg / lamivudine 300 mg / raltegravir 800 mg

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  • Adult patients (at least 18 years old)
  • Plasma HIV RNA > 1000 copies/ml
  • HIV-1-infection confirmed by ELISA and Western blot or Immunofluorescence
  • ART naïve patients or
  • ART for less than 3 months and more than 6 months ago ; an HIV resistance genotype at baseline showing no mutation to NNRTI and TDF or 3TC will be required
  • For women of childbearing age, negative urinary test for pregnancy and to accept contraceptive methods: condom use and intra-uterine device when possible or declare no wish of pregnancy in the coming year.
  • Confirmed or probable TB
  • TB treatment including rifampin started since 2 to 8 weeks before randomisation
  • Signed informed consent form
  • For French patients, to be affiliated to the National Health Care System


Exclusion Criteria:
  • HIV-2 infection (single or with HIV-1)
  • Woman who is pregnant or likely to become so, is breastfeeding or refuses to use contraception
  • ALT>2.5N, Hb <7g/dl, neutrophils < 750/mm3, platelet<50 000/mm3, bilirubin >5N, lipase >3N
  • Creatinine clearance <60ml/min as assessed by the Cockcroft method
  • Ongoing psychiatric pathology or any condition (including, but not limited to, the consumption of alcohol or drugs) which might, in the investigator's opinion, compromise the safety of treatment and/or patient compliance with the protocol
  • Concomitant treatments including phenytoin or phenobarbital (compounds interacting with UGT1A1)
  • Prior TB with a Mycobacterium tuberculosis strain resistant to rifampin
  • TB treatment started for more than 8 weeks before randomisation

contacts and locations

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: NCT00822315

Locations

Brazil
Hospital Genral de Nova Iguaçu
Nova Iguaçu, Brazil
Hospital Nossa Senhora da Coceiçao
Porto alegre, Brazil
Hospital Sanatorio Pertenon
Porto Alegre, Brazil
Ipec/Fiocruz
Rio de Janeiro, Brazil
Hospitral Universitario Pr Edgar Santos
Salvador da Bahia, Brazil
STD/AIDS department
Sao Paulo, Brazil
France
Hôpital Lariboisière
Paris, France, 75010
Hôpital Saint-Louis
Paris, France, 75010
CHI Villeneuve Saint Georges
Villeneuve Saint Georges, France, 94195

Sponsors and Collaborators

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

Investigators

Study Chair: Beatriz Grinsztejn, MD Fiocruz, Rio de Janiero, Brazil
Study Chair: Jean-Michel Molina, MD Hôpital Saint-Louis, Paris, France
More Information

More Information


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: NCT00822315   History of Changes  
Other Study ID Numbers: ANRS 12180 REFLATE TB  
Study First Received: January 13, 2009  
Last Updated: July 16, 2013  

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

HIV
Tuberculosis
Pharmacokinetics
Raltegravir
France
Brazil
treatment naive

Additional relevant MeSH terms:
HIV Infections
Tuberculosis
Tenofovir
Lamivudine
Raltegravir Potassium
Efavirenz
Rifampin

ClinicalTrials.gov processed this data on October 16, 2017
This information is provided by ClinicalTrials.gov.