RRHT: Rifampicin vs Rifabutin in HIV/AIDS Patients Combined With Tuberculosis

Sponsor

Shanghai Public Health Clinical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT03478033

Collaborator

The Guangxi Zhuang Autonomous Region Longtan hospital (Other), The Fourth People's Hospital of Nanning (Other), Shenzhen Third People's Hospital (Other), Yunnan Provincial Infectious Disease Hospital (Other), Zhejiang University (Other), Chongqing Public Health Medical Center (Other)

230

Enrollment

Location

Arms

32.6

Anticipated Duration (Months)

7.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To compared the efficacy and safety of rifampicin and rifabutin which included in the standard treatment of anti-tuberculosis in HIV/AIDs patients combined with pulmonary tuberculosis, a multi-center, prospective cohort will be established. Antiviral efficacy and drug drug interaction will be investigated in order to provide optimized treatment for HIV/AIDs with tuberculosis.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis, Pulmonary AIDS	Drug: Rifampicin Drug: Rifabutin	N/A

Detailed Description

Two hundreds and thirty participants will be randomly assigned to receive an anti--tuberculosis treatment include rifampicin or rifabutin for two months of intensive therapy. Isoniazid and rifampicin (or rifabutin) will be continued to use for four months of consolidation therapy. A total of followed up period will be 12 months.

The antiretroviral therapy（ART） include:

Tenofovir disoproxil fumarate 300mg/d +Lamivudine 300mg/d+ Efavirenz 600mg/d; or Zidovudine 300mg bid +Lamivudine 300mg/d +Efavirenz 600mg/d.

ART will be started after 2 weeks of anti-tuberculosis.

The follow-up visits include 2th, 4th, 6th, 8th, 12th,16th, 20th, 24th, 32th, 36th, 40th, 44th and 48th week. sputum smear, sputum culture, chest X-ray, CD4 Lymphocyte counts,HIV viral load and adverse event will be tested and recorded.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

230 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participates are assigned to one of two groups in parallel for the duration of the study.Participates are assigned to one of two groups in parallel for the duration of the study.

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Efficacy and Safety Evaluation of Standardized Treatment Included Rifampicin or Rifabutin in HIV/AIDs Patients Combined With Pulmonary Tuberculosis. A Prospective Study.

Actual Study Start Date :

Apr 15, 2018

Anticipated Primary Completion Date :

Jun 1, 2020

Anticipated Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Rifampicin group Rifampicin group: Intensive treatment（4 types of anti-TB medicines）for 2 months, then isoniazid and rifampicin for 4 months of consolidation therapy. isoniazid: 10-15mg/kg rifampicin: 10-20mg/kg pyrazinamide: 30-40mg/kg thambutol: 0.75(W<50kg)；1.0 g/d（W≥50kg）	Drug: Rifampicin Rifampicin capsules, 150mg Other Names: Rifampicin/INH/EMB/PZA
Experimental: Rifabutin group Rifabutin group: Intensive treatment（4 types anti-TB medicines）for 2 months,then isoniazid and rifabutin for 4 months of consolidation therapy. isoniazid: 10-15mg/kg rifabutin: 0.45g/d(W<50kg); 0.6g/d( W≥50kg） pyrazinamide: 30-40mg/kg thambutol: 0.75(W<50kg)；1.0 g/d（W≥50kg）	Drug: Rifabutin Rifabutin capsules, 150mg Other Names: Rifabutin/INH/EMB/PZA

Arm

Intervention/Treatment

Active Comparator: Rifampicin group

Rifampicin group: Intensive treatment（4 types of anti-TB medicines）for 2 months, then isoniazid and rifampicin for 4 months of consolidation therapy. isoniazid: 10-15mg/kg rifampicin: 10-20mg/kg pyrazinamide: 30-40mg/kg thambutol: 0.75(W<50kg)；1.0 g/d（W≥50kg）

Drug: Rifampicin

Rifampicin capsules, 150mg

Other Names:

Rifampicin/INH/EMB/PZA

Experimental: Rifabutin group

Rifabutin group: Intensive treatment（4 types anti-TB medicines）for 2 months,then isoniazid and rifabutin for 4 months of consolidation therapy. isoniazid: 10-15mg/kg rifabutin: 0.45g/d(W<50kg); 0.6g/d( W≥50kg） pyrazinamide: 30-40mg/kg thambutol: 0.75(W<50kg)；1.0 g/d（W≥50kg）

Drug: Rifabutin

Rifabutin capsules, 150mg

Other Names:

Rifabutin/INH/EMB/PZA

Outcome Measures

Primary Outcome Measures

The rate of sputum negative conversion [2~24 weeks]
The rate of the patients whose mycobacterium tuberculosis cannot be detected in sputum smear or bacteria culture.
Case fatality rate [12 months]
The number of deaths during follow-up caused by HIV/AIDS and TB / the number of patients with HIV/AIDs and TB enrolled in this study * 100%.

Secondary Outcome Measures

Treatment completion status [12 months]
The rate of patients who complete the whole anti-tuberculous treatment.
The percentage of HIV viral load less than the detection limit [6 months and 12 months]
The percentage of HIV viral load less than the detection limit
AE [12 months]
The number and severity of adverse event.
Time of sputum negative conversion [2~24 weeks]
The time of sputum negative conversion.
Chest CT scans improvement [2~24 weeks]
Chest CT showed tuberculosis lesion absorption

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age: 18-65 years old;
No limited to gender;
If anti-HIV-1 positive samples are detected by an initial test based on the ELISA method, they should be confirmed by western blot;
The patients who are diagnosed with pulmonary TB (mycobacterium tuberculosis of sputum smear or culture was positive) but had never be treated;
Sign informed consent form voluntarily, and guarantee to attend follow-up visits;
Do not have plan to remove from the current experimental site during the trial process;
The patients do not receive any antiretroviral treatment before;
The overall situation of the patient should not affect the assessment and completion of the trial.

Exclusion Criteria:

Patients with acute infection;
During the screening period，patients with combined opportunistic infections and instability (National HIV/AIDS treatment guidelines) except for tuberculosis, or combined malignancy;
During the screening period，hemachrome < 6 g/dl, leukocyte < 2000 /µl, neutrophils < 1000 /µl, platelet count < 75000 /µl, blood amylase is greater than two times the upper limit of normal, Scr is greater than1.5 times the upper limit of normal, AST/ALT/AKP is greater than two times the upper limit of normal, TBIL is greater than two times the upper limit of normal, serum CK is greater than two times the upper limit of normal;
Now suffering from acute or chronic pancreatitis;
Now suffering from peripheral neuritis;
Pregnant and lactating women;
Patients with severe mental and neurological diseases;
Drug users；
Patients with history of heavy drinking and cannot be terminated;
Serious gastrointestinal ulcers；
Atherosclerosis affects the arteries in the heart, brain or kidneys；
Non-Chinese nationality；
Now suffering from myopathy；
Patients with previously treated tuberculosis.