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

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

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.

Study Overview

• Status: Unknown
• Conditions: Tuberculosis, Pulmonary; AIDS
• Intervention / Treatment: Drug: Rifabutin; Drug: Rifampicin

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 Type: Interventional
• Enrollment (Anticipated): 230
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hongzhou Lu, PhD，MD; Phone Number: 3222 86-021-37990333; Email: luhongzhou@fudan.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201508
      • Recruiting
      • Shanghai Public Health Clinical Center
      • Contact: Yingzhong Shen, PhD，MD; Phone Number: 3222 86-021-37990333; Email: 027465@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Patients with acute infection;
2. During the screening period，patients with combined opportunistic infections and instability (National HIV/AIDS treatment guidelines) except for tuberculosis, or combined malignancy;
3. 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;
4. Now suffering from acute or chronic pancreatitis;
5. Now suffering from peripheral neuritis;
6. Pregnant and lactating women;
7. Patients with severe mental and neurological diseases;
8. Drug users；
9. Patients with history of heavy drinking and cannot be terminated;
10. Serious gastrointestinal ulcers；
11. Atherosclerosis affects the arteries in the heart, brain or kidneys；
12. Non-Chinese nationality；
13. Now suffering from myopathy；
14. Patients with previously treated tuberculosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of sputum negative conversion	The rate of the patients whose mycobacterium tuberculosis cannot be detected in sputum smear or bacteria culture.	2~24 weeks
Case fatality rate	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%.	12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shanghai Public Health Clinical Center
• Collaborators: Zhejiang University; Yunnan Provincial Infectious Disease Hospital; Shenzhen Third People's Hospital; Chongqing Public Health Medical Center; The Fourth People's Hospital of Nanning; The Guangxi Zhuang Autonomous Region Longtan hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 15, 2018
• Primary Completion (ANTICIPATED): June 1, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (ACTUAL): March 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2018
• Last Update Submitted That Met QC Criteria: April 23, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Tuberculosis; AIDS; Rifabutin; Rifampicin
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Rifabutin
• Other Study ID Numbers: 2017ZX10202101-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No