NCT00651066

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P25-P50 for phase_2 hiv-infections

Timeline
Completed

Started Jun 2010

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 28, 2008

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 2, 2008

Completed
2.2 years until next milestone

Study Start

First participant enrolled

June 1, 2010

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2012

Completed
Last Updated

July 17, 2013

Status Verified

July 1, 2013

Enrollment Period

2.3 years

First QC Date

March 28, 2008

Last Update Submit

July 16, 2013

Conditions

Keywords

HIVTuberculosisRifabutinPharmacokineticsVietnam

Outcome Measures

Primary Outcomes (1)

  • 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)

    2, 5 and 8 weeks after randomisation

Secondary Outcomes (2)

  • Area under the curve (AUC) of lopinavir/ritonavir in combination with two doses of rifabutine

    5 and 8 weeks after randomisation

  • Safety : proportion of patients with grade 3 and grade 4 adverse events

    through out the trial

Study Arms (2)

1

EXPERIMENTAL

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

Drug: rifabutin in combination with lopinavir boosted by ritonavir - dosing schedule 1

2

EXPERIMENTAL

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

Drug: rifabutin in combination with lopinavir boosted by ritonavir - dosing schedule 2

Interventions

3TC(300mg)/D4t(60mg)/LPV/r(800mg/200mg)+INH/PZA/EMT/Rifabutin(150 mg TPW 3 wks switch to 150 mg OD 4 wks);

1

3TC(300mg)/D4t(60mg)/LPV/r(800mg/200mg)+INH/PZA/EMT/Rifabutin(150 mg OD 3 wks switch to 150 mg TPW 4 wks);

2

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Pulmonary tuberculosis defined as either
  • at least 2 sputum smears positive for AFB
  • sputum smear positive for AFB and a chest radiograph compatible with active tuberculosis
  • 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%

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Pham Ngoc Tach Hospital

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

HIV InfectionsTuberculosis

Interventions

Rifabutin

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesMycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

RifamycinsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsLactams, MacrocyclicMacrocyclic CompoundsPolycyclic Compounds

Study Officials

  • Anthony D. Harries, PhD

    The international Union Against Tuberculosis and Lung Diseases (IUATLD), Paris, France

    PRINCIPAL INVESTIGATOR
  • Huy Dung Nguyen, MD

    Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 28, 2008

First Posted

April 2, 2008

Study Start

June 1, 2010

Primary Completion

September 1, 2012

Study Completion

September 1, 2012

Last Updated

July 17, 2013

Record last verified: 2013-07

Locations