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

This study has been completed.
Sponsor:
Collaborators:
Gilead Sciences
Merck
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: January 17, 2013
Last verified: January 2013
History of Changes
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

U.S. FDA Resources

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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Evolution in HIV RNA and HIV DNA (total and 2 LTR circular) from baseline to week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Evolution of CD4 cell counts from baseline to week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Frequency, type and time to a new AIDS-defining event or death [ Time Frame: Through out the trial ] [ Designated as safety issue: Yes ]
  • Frequency, type, time to grade 3 or 4 adverse event [ Time Frame: Through out the trial ] [ Designated as safety issue: Yes ]
  • Rate of success of TB treatment [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Anti-TB resistance rate [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Evolution of raltegravir and efavirenz trough concentration [ Time Frame: Through out the trial ] [ Designated as safety issue: No ]

Enrollment: 155
Study Start Date: July 2009
Study Completion Date: June 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00822315

Locations
Brazil
Hospital Genral de Nova Iguaçu
Nova Iguaçu, Brazil
Hospital Sanatorio Pertenon
Porto Alegre, Brazil
Hospital Nossa Senhora da Coceiçao
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
Investigators
Study Chair: Beatriz Grinsztejn, MD Fiocruz, Rio de Janiero, Brazil
Study Chair: Jean-Michel Molina, MD Hôpital Saint-Louis, Paris, France
  More 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: NCT00822315     History of Changes
Other Study ID Numbers: ANRS 12180 REFLATE TB
Study First Received: January 13, 2009
Last Updated: January 17, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Brazil: Ministry of Health

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
Acquired Immunodeficiency Syndrome
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
 Bacterial Infections
Rifampin
Lamivudine
Efavirenz
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on March 03, 2013