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Clinical Trials

MainTitle

Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in Patients With TB/HIV Co-infection in South Africa

This study has been completed
Sponsor
French National Agency for Research on AIDS and Viral Hepatitis


Information provided by (Responsible Party)
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier
NCT00640887

First received: February 6, 2008
Last updated: June 17, 2011
Last Verified: June 2011
History of Changes
Purpose

Purpose

The overall aim of the project is to evaluate rifabutin (RBT) as a replacement for rifampicin (RMP), for the combined treatment of tuberculosis and HIV infection. RBT represents an alternative to RMP for HIV infected patients as its half-life is longer and the enzymatic induction effect appears to be less important on the associated antiretroviral therapy (ART) drugs.

This phase II trial is to determine precisely the pharmacokinetics parameters of RBT in combination with different ART regimens in Vietnamese HIV infected patients with pulmonary tuberculosis, in order to define optimal doses that will be further tested in a larger phase III trial comparing safety, tolerability and efficacy of RBT and RMP regimens.

Condition Intervention Phase
HIV Infections
Tuberculosis

Drug : rifabutin in combination with efavirenz
Drug : rifabutin in combination with nevirapine
Drug : rifabutin in combination with lopinavir/ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in the Treatment of Tuberculosis Patient With HIV Infection in South Africa: A Phase II Trial

Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures

  • Area under the curve (AUC) of rifabutine measured (a)before introduction of ART;(b)after ART initiation (two different doses of RBT in combination with efavirenz, nevirapine or lopinavir/ritonavir) [ Time Frame: 2, 6 and 10 weeks after randomisation ]
Secondary Outcome Measures:
  • Area under the curve (AUC) of efavirenz, nevirapine and lopinavir/ritonavir in combination with two doses of rifabutine [ Time Frame: 6 and 10 weeks after randomisation ]
  • Safety : proportion of patients with grade 3 and grade 4 adverse events [ Time Frame: through out the trial ]

Enrollment: 48
Study Start Date: February 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: 1
RBT associated with EFV based ART
Drug: rifabutin in combination with efavirenz
    Ia. arm 1a:
    • D4T/3TC/EFV(600mg)+INH/Rifabutin(450 mg OD 4 wks switch to 600 mg OD 4 wks);
    Ib. arm 1b:
    • D4T/3TC/EFV(600mg)+INH/Rifabutin(600 mg OD 4 wks switch to 450 mg OD 4 wks);

    Experimental: 2
    RBT associated with NVP based ART
    Drug: rifabutin in combination with nevirapine
      IIa. arm 2a:
      • D4T/3TC/NVP(200mg)+INH/Rifabutin(300 mg OD 4 wks switch to 450 mg OD 4 wks);
      IIb. arm 2b :
      • D4T/3TC/NVP(200mg)+INH/Rifabutin(450 mg OD 4 wks switch to 300 mg OD 4 wks);

      Experimental: 3
      RBT associated with LPV/r based ART
      Drug: rifabutin in combination with lopinavir/ritonavir
        IIIa. arm 3a :
        • D4T/3TC/LPV/r(2 tabs BD)+INH/Rifabutin(150 mg TPW 4 wks switch to 150 mg OD 4 wks);
        IIIb. arm 3b:
        • D4T/3TC/LPV/r(2 tabs BD)+INH/Rifabutin(150 mg OD 4 wks switch to 150 mg TPW 4 wks).

        Detailed Description:

        Patients will be offered to participated in the study after the first 6 weeks of the nationally recommended TB treatment. All the enrolled patients will be switched to rifabutin and randomized, two weeks later, to one of the three study ARV regimens. The RBT doses will be then adapted to the allocated ARV regimen according to a cross over scheme. Three full pharmacokinetics profile will be performed at different time point : before initiation of ARV, after one month of the first RFB dosage and one month after the second RFB dosage.

        Eligibility

        Eligibility

        Ages Eligible for Study: 18 Years to 65 Years  
        Sexes Eligible for Study: All  
        Accepts Healthy Volunteers: No  

        Criteria

        Inclusion Criteria:

        • Pulmonary tuberculosis (proven by AFB positive sputum or culture)
        • Having completed and adhered to 6 wks of intensive phase TB chemotherapy
        • Positive HIV antibody and CD4 count >50 /mm3 and <=200
        • Weight > 50 kg
        • No ART in the preceding 3 months
        • No more than 2 weeks or ART previously
        • No grade 3 or 4 clinical or laboratory findings
        • Negative pregnancy test and appropriate contraceptive measures during the duration of the trial for female of childbearing age
        • Having a firm home address that is readily accessible
        • Karnofsky score>=80%


        Exclusion Criteria:
        • History of TB within the 3 years preceding the presenting episode of TB
        • Previous treatment for MDR TB
        • Concomitant OI requiring additional anti-infectious treatment
        • Formal contraindication to any drug used in the trial
        • Diabetes mellitus requiring drug treatment
        • Recreational drug or alcohol abuse
        • History of drug hypersensitivity to TB or related medications
        • Interrupted TB therapy for more than 1 week
        • Less than 90% adherent to first 6 weeks of intensive phase chemotherapy
        • Mental illness that could impair ability to give informed consent or result in poor adherence to trial protocol and therapy
        • Neutropenia <1200 /L, anaemia <6.8 g/dL, liver function test > grade 2
        • Requiring concomitant medications that may potentially interact with study drugs
        • Pregnant or lactating women
        • Karnofsky score >80%
        • Any condition rendering the patient unable to understand the nature, scope, and
        possible consequences of thes study and to provide consent

        contacts and locations

        Contacts and Locations

        Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

        Please refer to this study by its ClinicalTrials.gov identifier: NCT00640887

        Locations

        South Africa
        Unit for Clinical and Biomedical TB Research (Medical Research Council)
        Durban, South Africa, 4067

        Sponsors and Collaborators

        French National Agency for Research on AIDS and Viral Hepatitis

        Investigators

        Principal Investigator: Anthony D Harries, MD, PhD The international Union Against Tuberculosis and Lung Diseases (IUATLD), Paris, France
        Principal Investigator: Alexander PYM, MD Medical Research Council, South Africa
        More Information

        More Information


        Responsible Party: Claire Rekacewicz, French National Agency for Research on AIDS and Viral Hepatitis  
        ClinicalTrials.gov Identifier: NCT00640887   History of Changes  
        Other Study ID Numbers: ANRS12150a  
        Study First Received: February 6, 2008  
        Last Updated: June 17, 2011  

        Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:

        HIV
        Tuberculosis
        Rifabutin
        Pharmacokinetics
        South Africa

        Additional relevant MeSH terms:
        Infection
        Communicable Diseases
        HIV Infections
        Acquired Immunodeficiency Syndrome
        Tuberculosis
        Ritonavir
        Lopinavir
        Nevirapine
        Efavirenz
        Rifabutin

        ClinicalTrials.gov processed this data on October 16, 2017
        This information is provided by ClinicalTrials.gov.