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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00822315
• Other study ID #: ANRS 12180 REFLATE TB
• Status: Completed
• Phase: Phase 2
• First received: January 13, 2009
• Last updated: July 16, 2013
• Start date: July 2009
• Est. completion date: May 2012

Study information

• Verified date: July 2013
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Brazil: Ministry of Health
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: May 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

Drug:
• efavirenz
tenofovir 245 mg / lamivudine 300 mg / efavirenz 600 mg
• raltegravir
tenofovir 245 mg / lamivudine 300 mg / raltegravir 400 mg
• raltegravir
tenofovir 245 mg / lamivudine 300 mg / raltegravir 800 mg

Locations

Country	Name	City	State
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
France	Hôpital Lariboisière	Paris
France	Hôpital Saint-Louis	Paris
France	CHI Villeneuve Saint Georges	Villeneuve Saint Georges

Sponsors (3)

Lead Sponsor	Collaborator
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.

Countries where clinical trial is conducted

Brazil,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Evolution in HIV RNA and HIV DNA (total and 2 LTR circular) from baseline to week 48		48 weeks	No
Secondary	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	No
Secondary	Evolution of CD4 cell counts from baseline to week 48		48 weeks	No
Secondary	Frequency, type and time to a new AIDS-defining event or death		Through out the trial	Yes
Secondary	Frequency, type, time to grade 3 or 4 adverse event		Through out the trial	Yes
Secondary	Rate of success of TB treatment		48 weeks	No
Secondary	Anti-TB resistance rate		48 weeks	No
Secondary	Evolution of raltegravir and efavirenz trough concentration		Through out the trial	No