NCT00822315

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
155

participants targeted

Target at P50-P75 for phase_2 hiv-infections

Timeline
Completed

Started Jul 2009

Geographic Reach
2 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 13, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 14, 2009

Completed
6 months until next milestone

Study Start

First participant enrolled

July 1, 2009

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2011

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2012

Completed
Last Updated

July 17, 2013

Status Verified

July 1, 2013

Enrollment Period

2.3 years

First QC Date

January 13, 2009

Last Update Submit

July 16, 2013

Conditions

HIV InfectionsTuberculosis

Keywords

HIVTuberculosisPharmacokineticsRaltegravirFranceBraziltreatment naive

Outcome Measures

Primary Outcomes (1)

  • 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

    24 weeks

Secondary Outcomes (10)

  • 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

    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

    24 and 48 weeks

  • Evolution in HIV RNA and HIV DNA (total and 2 LTR circular) from baseline to week 48

    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

    At the time of virologic failure

  • Evolution of CD4 cell counts from baseline to week 48

    48 weeks

  • +5 more secondary outcomes

Study Arms (3)

1

ACTIVE COMPARATOR

efavirenz

Drug: efavirenz

2

EXPERIMENTAL

raltegravir 400 mg

Drug: raltegravir

3

EXPERIMENTAL

raltegravir 800 mg

Drug: raltegravir

Interventions

efavirenzDRUG

tenofovir 245 mg / lamivudine 300 mg / efavirenz 600 mg

1
raltegravirDRUG

tenofovir 245 mg / lamivudine 300 mg / raltegravir 400 mg

2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Hospital Genral de Nova Iguaçu

Nova Iguaçu, Brazil

Location

Hospital Nossa Senhora da Coceiçao

Porto Alegre, Brazil

Location

Hospital Sanatorio Pertenon

Porto Alegre, Brazil

Location

Ipec/Fiocruz

Rio de Janeiro, Brazil

Location

Hospitral Universitario Pr Edgar Santos

Salvador, Brazil

Location

STD/AIDS department

São Paulo, Brazil

Location

Hôpital Lariboisière

Paris, 75010, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

CHI Villeneuve Saint Georges

Villeneuve-Saint-Georges, 94195, France

Location

Related Publications (1)

  • Grinsztejn B, De Castro N, Arnold V, Veloso VG, Morgado M, Pilotto JH, Brites C, Madruga JV, Barcellos NT, Santos BR, Vorsatz C, Fagard C, Santini-Oliveira M, Patey O, Delaugerre C, Chene G, Molina JM; ANRS 12 180 Reflate TB study group. Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 Reflate TB): a multicentre, phase 2, non-comparative, open-label, randomised trial. Lancet Infect Dis. 2014 Jun;14(6):459-67. doi: 10.1016/S1473-3099(14)70711-X. Epub 2014 Apr 9.

    PMID: 24726095DERIVED

MeSH Terms

Conditions

HIV InfectionsTuberculosis

Interventions

efavirenzRaltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

PyrrolidinonesPyrrolidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Beatriz Grinsztejn, MD

    Fiocruz, Rio de Janiero, Brazil

    STUDY CHAIR

  • Jean-Michel Molina, MD

    Hôpital Saint-Louis, Paris, France

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 13, 2009

First Posted

January 14, 2009

Study Start

July 1, 2009

Primary Completion

November 1, 2011

Study Completion

May 1, 2012

Last Updated

July 17, 2013

Record last verified: 2013-07

Locations

FR(3)BR(6)