NCT00822315CompletedPhase 2
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
ANRS, Emerging Infectious Diseases9 sites in 2 countries155 target enrollmentStarted: July 2009Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 155
- Locations
- 9
- Primary Endpoint
- 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
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
1
Active Comparator
efavirenz
Intervention: efavirenz (Drug)
2
Experimental
raltegravir 400 mg
Intervention: raltegravir (Drug)
3
Experimental
raltegravir 800 mg
Intervention: raltegravir (Drug)
Outcomes
Primary Outcomes
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 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(24 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)
- 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)
- Evolution of CD4 cell counts from baseline to week 48(48 weeks)
- Frequency, type and time to a new AIDS-defining event or death(Through out the trial)
- Anti-TB resistance rate(48 weeks)
- Evolution of raltegravir and efavirenz trough concentration(Through out the trial)
- Frequency, type, time to grade 3 or 4 adverse event(Through out the trial)
- Rate of success of TB treatment(48 weeks)
Investigators
Study Sites (9)
Loading locations...
Similar Trials
Completed
Phase 3
Raltegravir Versus Efavirenz in Naive HIV-1-infected Patients Receiving Rifampin for Active TuberculosisHIV-1 InfectionTuberculosisNCT02273765ANRS, Emerging Infectious Diseases460
Completed
Phase 3
A Study to Evaluate the Safety and Efficacy of Raltegravir (MK0518) in HIV-Infected Patients Failing Current Antiretroviral Therapies (MK0518-018 EXT2)HIV InfectionsNCT00293267Merck Sharp & Dohme LLC352
Completed
Not Applicable
RAL-eve Study: Raltegravir Substitution StudyHIV InfectionsNCT00523237Stanford University14
Completed
Phase 1
The Raltegravir and Ribavirin Pharmacokinetics (PK) StudyHIV InfectionsNCT00982553Imperial College London14
Completed
Phase 2
Capacity of the Dual Combination Raltegravir/Etravirine to Maintain Virological Success in HIV-1 Infected Patients of at Least 45 Years of Age- ANRS 163 ETRALHIV-1 InfectionNCT02212379ANRS, Emerging Infectious Diseases170