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

Primary Purpose

HIV Infections, Tuberculosis

Status
Completed
Phase
Phase 2
Locations
Vietnam
Study Type
Interventional
Intervention
rifabutin in combination with lopinavir boosted by ritonavir - dosing schedule 1
rifabutin in combination with lopinavir boosted by ritonavir - dosing schedule 2
Sponsored by
French National Agency for Research on AIDS and Viral Hepatitis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, Tuberculosis, Rifabutin, Pharmacokinetics, Vietnam

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Pulmonary tuberculosis defined as either

    • at least 2 sputum smears positive for AFB
    • 1 sputum smear positive for AFB and a chest radiograph compatible with active tuberculosis
    • 1 sputum culture positive and and a chest radiograph compatible with active tuberculosis
    • a clinical history and chest radiograph compatible with active tuberculosis and 2 sputum smear negative for AFB
  • Positive HIV antibody and CD4 count <=250 /mm3
  • Weight > 40 kg
  • No history of ART
  • 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 or MDR TB treatment
  • 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

Sites / Locations

  • Pham Ngoc Tach Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

RBT (150 mg TPW during 3 weeks switch to 150mg OD for the following 3 weeks) associated with LPV/r based ART

RBT (150 mg OD during 3 weeks switch to 150mg TPW for the following 3 weeks) associated with LPV/r based ART

Outcomes

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 lopinavir/ritonavir)

Secondary Outcome Measures

Area under the curve (AUC) of lopinavir/ritonavir in combination with two doses of rifabutine
Safety : proportion of patients with grade 3 and grade 4 adverse events

Full Information

First Posted
March 28, 2008
Last Updated
July 16, 2013
Sponsor
French National Agency for Research on AIDS and Viral Hepatitis
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1. Study Identification

Unique Protocol Identification Number
NCT00651066
Brief Title
Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in Patients With TB/HIV Co-infection in Vietnam
Official Title
Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in the Treatment of Tuberculosis Patient With HIV Infection in Vietnam : A Phase II Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
French National Agency for Research on AIDS and Viral Hepatitis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
Patients will be offered to participated in the study when they start TB treatment. All the enrolled patients will immediately be switched to rifabutin and randomized, to one of the RBT doses that will be then adapted to the allocated RBT regimen according to a cross over scheme. Three full pharmacokinetics profile will be performed at different time point : before initiation of ARV, after three weeks of the first RBT dosage and after three weeks of the secondRBT dosage. Patients will then be referred to the national program for further treatment. A follow-up visit will be planned at the end of the antiTB treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Tuberculosis
Keywords
HIV, Tuberculosis, Rifabutin, Pharmacokinetics, Vietnam

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
RBT (150 mg TPW during 3 weeks switch to 150mg OD for the following 3 weeks) associated with LPV/r based ART
Arm Title
2
Arm Type
Experimental
Arm Description
RBT (150 mg OD during 3 weeks switch to 150mg TPW for the following 3 weeks) associated with LPV/r based ART
Intervention Type
Drug
Intervention Name(s)
rifabutin in combination with lopinavir boosted by ritonavir - dosing schedule 1
Intervention Description
3TC(300mg)/D4t(60mg)/LPV/r(800mg/200mg)+INH/PZA/EMT/Rifabutin(150 mg TPW 3 wks switch to 150 mg OD 4 wks);
Intervention Type
Drug
Intervention Name(s)
rifabutin in combination with lopinavir boosted by ritonavir - dosing schedule 2
Intervention Description
3TC(300mg)/D4t(60mg)/LPV/r(800mg/200mg)+INH/PZA/EMT/Rifabutin(150 mg OD 3 wks switch to 150 mg TPW 4 wks);
Primary Outcome Measure Information:
Title
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 lopinavir/ritonavir)
Time Frame
2, 5 and 8 weeks after randomisation
Secondary Outcome Measure Information:
Title
Area under the curve (AUC) of lopinavir/ritonavir in combination with two doses of rifabutine
Time Frame
5 and 8 weeks after randomisation
Title
Safety : proportion of patients with grade 3 and grade 4 adverse events
Time Frame
through out the trial

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pulmonary tuberculosis defined as either at least 2 sputum smears positive for AFB 1 sputum smear positive for AFB and a chest radiograph compatible with active tuberculosis 1 sputum culture positive and and a chest radiograph compatible with active tuberculosis a clinical history and chest radiograph compatible with active tuberculosis and 2 sputum smear negative for AFB Positive HIV antibody and CD4 count <=250 /mm3 Weight > 40 kg No history of ART 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 or MDR TB treatment 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony D. Harries, PhD
Organizational Affiliation
The international Union Against Tuberculosis and Lung Diseases (IUATLD), Paris, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Huy Dung Nguyen, MD
Organizational Affiliation
Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pham Ngoc Tach Hospital
City
Ho Chi Minh City
Country
Vietnam

12. IPD Sharing Statement

Citations:
PubMed Identifier
24465443
Citation
Lan NT, Thu NT, Barrail-Tran A, Duc NH, Lan NN, Laureillard D, Lien TT, Borand L, Quillet C, Connolly C, Lagarde D, Pym A, Lienhardt C, Dung NH, Taburet AM, Harries AD. Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam. PLoS One. 2014 Jan 22;9(1):e84866. doi: 10.1371/journal.pone.0084866. eCollection 2014.
Results Reference
derived

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

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