Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in the Treatment of Tuberculosis Patient With HIV Infection in South Africa: A Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- 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)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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%
排除标准
- •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
研究组 & 干预措施
1
RBT associated with EFV based ART
干预措施: rifabutin in combination with efavirenz (Drug)
2
RBT associated with NVP based ART
干预措施: rifabutin in combination with nevirapine (Drug)
3
RBT associated with LPV/r based ART
干预措施: rifabutin in combination with lopinavir/ritonavir (Drug)
结局指标
主要结局
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)
时间窗: 2, 6 and 10 weeks after randomisation
次要结局
- Area under the curve (AUC) of efavirenz, nevirapine and lopinavir/ritonavir in combination with two doses of rifabutine(6 and 10 weeks after randomisation)
- Safety : proportion of patients with grade 3 and grade 4 adverse events(through out the trial)