HIV InfectionsPhase 2NCT00822315
Efficacy and Safety of 2 Raltegravir Doses in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis
A Phase 2 study testing efavirenz and raltegravir in people with HIV Infections and Tuberculosis, run by ANRS, Emerging Infectious Diseases at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections, Tuberculosis
- What is being tested?
- efavirenz and raltegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Jul 2009to May 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
Brazil6 sites
Hospital Genral de Nova Iguaçu
Nova Iguaçu
Hospital Nossa Senhora da Coceiçao
Porto Alegre
Hospital Sanatorio Pertenon
Porto Alegre
Ipec/Fiocruz
Rio de Janeiro
Hospitral Universitario Pr Edgar Santos
Salvador
STD/AIDS department
São Paulo
France3 sites
Hôpital Lariboisière
Paris, 75010
Hôpital Saint-Louis
Paris, 75010
CHI Villeneuve Saint Georges
Villeneuve-Saint-Georges, 94195
About this study
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
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.
- Conditions
- HIV Infections, Tuberculosis
- Being tested
- efavirenz, raltegravir
- Keywords
- HIV, Tuberculosis, Pharmacokinetics, Raltegravir, France, Brazil, treatment naive
- Medical subject headings
- HIV Infections, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
efavirenzDrug
tenofovir 245 mg / lamivudine 300 mg / efavirenz 600 mg
raltegravirDrug
tenofovir 245 mg / lamivudine 300 mg / raltegravir 400 mg
raltegravirDrug
tenofovir 245 mg / lamivudine 300 mg / raltegravir 800 mg
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | efavirenz Receives: Drug: efavirenz |
| 2 | Experimental | raltegravir 400 mg Receives: Drug: raltegravir |
| 3 | Experimental | raltegravir 800 mg Receives: Drug: raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 24 and 48 weeks
Evolution in HIV RNA and HIV DNA (total and 2 LTR circular) from baseline to week 48
Measured: 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
Measured: At the time of virologic failure
Evolution of CD4 cell counts from baseline to week 48
Measured: 48 weeks
Frequency, type and time to a new AIDS-defining event or death
Measured: Through out the trial
Frequency, type, time to grade 3 or 4 adverse event
Measured: Through out the trial
Rate of success of TB treatment
Measured: 48 weeks
Anti-TB resistance rate
Measured: 48 weeks
Evolution of raltegravir and efavirenz trough concentration
Measured: Through out the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2009 (estimated)
- Study startJul 2009
- Primary completionNov 2011
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by ANRS, Emerging Infectious DiseasesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- ANRS, Emerging Infectious Diseases
- Sponsor type
- Other government
- Collaborators
- Gilead Sciences, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Beatriz Grinsztejn, MD, Study chair, Fiocruz, Rio de Janiero, BrazilJean-Michel Molina, MD, Study chair, Hôpital Saint-Louis, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00822315
- Sponsor's protocol ID
- ANRS 12180 REFLATE TB
- Status last verified
- Jul 2013
- First submitted
- 13 Jan 2009
- Last updated
- 17 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24726095
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00822315
- Acronym / sponsor ID
- ANRS 12180 REFLATE TB
- Conditions
- HIV Infections, Tuberculosis
- Keywords
- HIV, Tuberculosis, Pharmacokinetics, Raltegravir, France, Brazil, treatment naive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 155 participants (actual)
- Lead sponsor
- ANRS, Emerging Infectious DiseasesOther government
- Collaborators
- Gilead Sciences, Merck Sharp & Dohme LLC
- Study start
- Jul 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 14 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: efavirenzefavirenz |
| 2 | Experimental | Drug: raltegravirraltegravir 400 mg |
| 3 | Experimental | Drug: raltegravirraltegravir 800 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| efavirenztenofovir 245 mg / lamivudine 300 mg / efavirenz 600 mg | Drug | 1 |
| raltegravirtenofovir 245 mg / lamivudine 300 mg / raltegravir 400 mg | Drug | 2 |
| raltegravirtenofovir 245 mg / lamivudine 300 mg / raltegravir 800 mg | Drug | 3 |
Primary outcome
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
10 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2013.
- Derived from this study: PubMed 24726095Grinsztejn 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.
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beatriz Grinsztejn, MD study chair
Fiocruz, Rio de Janiero, Brazil
Jean-Michel Molina, MD study chair
Hôpital Saint-Louis, Paris, France
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing efavirenz and raltegravir in people with HIV Infections and Tuberculosis, run by ANRS, Emerging Infectious Diseases at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Brazil, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00822315, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2013.