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Comparing Daily vs Intermittent Regimen of ATT in HIV With Pulmonary Tuberculosis

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ClinicalTrials.gov Identifier: NCT00933790
Recruitment Status : Active, not recruiting
First Posted : July 7, 2009
Last Update Posted : April 28, 2017
Sponsor:
Information provided by (Responsible Party):
Narendran Gopalan, Tuberculosis Research Centre, India

Study Description
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Brief Summary:
Acquired Rifampicin Resistance has emerged as an important issue in the treatment of HIV-TB patients. It has not been a major problem in HIV-negative individuals treated for TB treated with standard intermittent regimens. The study would generate data on the efficacy of daily and thrice weekly regimen of ATT in pulmonary TB patients with HIV in the presence of highly active antiretroviral therapy (HAART). Not many trials have compared sputum conversion and adverse drug reaction between daily and intermittent regimens of ATT in HIV positive patients. This study provides a unique opportunity for comparison of daily and intermittent therapy for HIV patients with pulmonary TB looking into multiple dimensions of HIV-TB treatment namely efficacy, drug resistance, toxicity , drug interaction and immune reconstitution inflammatory syndrome. The primary outcome of the study is to compare the efficacy of three anti-TB regimens in a) reducing bacteriological failures and b) decreasing the emergence of Acquired Rifampicin Resistance (ARR). The secondary outcomes include unfavourable responses (clinical failures, deaths, relapses) as whole, treatment emergent adverse drug reactions, pharmacokinetic levels of ATT and incidence of immune reconstitution syndrome.

Condition or disease Intervention/treatment Phase
HIV Infection Pulmonary TB Drug: ATT (Ethambutol, Pyrazinamide, INH, Rifampicin) Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 331 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Clinical Trial Comparing Daily Vs. Intermittent 6 - Month Short Course Chemotherapy in Reducing Failures & Emergence of Acquired Rifampicin Resistance (ARR) in Patients With HIV and Pulmonary Tuberculosis
Actual Study Start Date : September 14, 2009
Actual Primary Completion Date : December 31, 2016
Estimated Study Completion Date : December 31, 2018

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Arms and Interventions
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Arm Intervention/treatment
Active Comparator: 2EHRZ3/4HR3
Regimen 3. Intermittent - 2EHRZ3/4HR3 (E 1200mg, H 600 mg, R 450/600 mg depending on Weight <60, 600 mg for 60 kg or more, Z 1500 mg given thrice weekly)
 Drug: ATT (Ethambutol, Pyrazinamide, INH, Rifampicin)
Ethambutol 800 mg for daily, 1200 mg for intermittent therapy, Pyrazinamide 1500 mg for both daily and intermittent, INH 300 mg for daily and 600 mg for intermittent therapy, Rifampicin 450 mg for both daily and intermittent therapy for patients below 60 kg, 600 mg for both daily and intermittent therapy for patients 60 kg and above
Other Names:
  • ATT
  • Rifampicin
Experimental: 2EHRZ7/4HR7
Regimen 1. Daily - 2EHRZ7/4HR7 (E 800 mg ,H 300 mg, R 450/600 mg depending on Weight <60, 600 mg for 60 kg or more, Z 1500 mg daily)
 Drug: ATT (Ethambutol, Pyrazinamide, INH, Rifampicin)
Ethambutol 800 mg for daily, 1200 mg for intermittent therapy, Pyrazinamide 1500 mg for both daily and intermittent, INH 300 mg for daily and 600 mg for intermittent therapy, Rifampicin 450 mg for both daily and intermittent therapy for patients below 60 kg, 600 mg for both daily and intermittent therapy for patients 60 kg and above
Other Names:
  • ATT
  • Rifampicin
Experimental: 2EHRZ7/4HR3
Regimen 2. Part Daily - 2EHRZ7/4HR3 (E 800 mg ,H 300 mg, R 450/600 mg depending on Weight <60, 600 mg for 60 kg or more, Z 1500 mg daily in the intensive phase followed by H-600 mg ,R-450/600 mg in the continuation phase thrice weekly)
 Drug: ATT (Ethambutol, Pyrazinamide, INH, Rifampicin)
Ethambutol 800 mg for daily, 1200 mg for intermittent therapy, Pyrazinamide 1500 mg for both daily and intermittent, INH 300 mg for daily and 600 mg for intermittent therapy, Rifampicin 450 mg for both daily and intermittent therapy for patients below 60 kg, 600 mg for both daily and intermittent therapy for patients 60 kg and above
Other Names:
  • ATT
  • Rifampicin


Outcome Measures
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Primary Outcome Measures :
  1. unfavourable responses during treatment [ Time Frame: At the end of 6 months ]
    including bacteriological and failures and ARR, clinical failures, TEADRS requiring premanent discontinuation of the drug , Deaths except unnatural and Defaults during treatment period


Secondary Outcome Measures :
  1. Unfavorable responses during follow-up [ Time Frame: At the end of 6 months and at the end of follow-up of 1 year ]
    recurrences and deaths during follow up

  2. TEADR's between the groups [ Time Frame: At the end of 6 months and at the end of follow-up of 1 year ]
  3. Incidence of Immune Reconstitution Syndrome among the groups [ Time Frame: At the end of 6 months and at the end of follow-up of 1 year ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age above 18 years.
  • HIV-1/2 infected patients with Pulmonary TB. This includes sputum smear positive disease.
  • Initially smear negative but Xpert-MTB positive or LPA positive taken as a surrogate marker for culture positivity (e.g. miliary TB, Mediastinal adenitis and Chest x-ray with persistent abnormality after antibiotics). as BACTEC (Becton-Dickinson) has been phased out ,Final inclusion will only be patients positive by LJ culture
  • Persistent X-ray abnormality will be included for allocation. However final inclusion into both ITT and efficacy analysis will depend on positivity in LJ culture.
  • Living within 40 km radius from the nearest sub centre of TRC and willing for attendance as prescribed.
  • Likely to remain in the same area for at least one and half years after start of treatment.
  • Willing for house visits and surprise checks.
  • Willing to participate and give informed consent after going through the terms and conditions of the trial.

Exclusion Criteria:

  • Patients with known hypersensitivity to rifampicin
  • Pregnancy and lactation at initial presentation
  • Major complications like HIV encephalopathy, renal dysfunction (serum creatinine > 1.5 mg% in the absence of dehydration) or jaundice (serum bilirubin > 2 mgs% along with SGOT /SGPT elevation > 2.5 times the upper limit of normal).
  • Previous anti-tuberculosis treatment for more than 1 month. Prophylaxis (non-rifampicin containing regimen) will not be considered as prior antituberculosis treatment.
  • Moribund, bedridden or unconscious patients.
  • Co-morbid conditions like uncontrolled diabetes mellitus, cardiac failure, and malignancy at initial presentation.
  • Major psychiatric illness.
  • Patients on second line ART, mainly protease inhibitors, at initial presentation.
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00933790


Locations
India
Tuberculosis Research Centre (ICMR)
Chennai, Tamil Nadu, India, 600 031
Govt. Hospital of Thoracic Medicine, Tambaram
Chennai, Tamil Nadu, India, 600 047
Tuberculosis Research Centre (ICMR)
Madurai, Tamil Nadu, India, 625 020
Sponsors and Collaborators
Tuberculosis Research Centre, India
Investigators
Principal Investigator: Narendran Gopalan, DNB (Chest) Scientist 'B', Tuberculosis Research Centre (ICMR), Chennai, India
Principal Investigator: Soumya Swaminathan, MD Scientist 'F', Tuberculosis Research Centre (ICMR), Chennai, India
More Information
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Additional Information:
Tuberculosis Research Centre (ICMR), India  This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Narendran Gopalan, Asst.Director, NIRT, Tuberculosis Research Centre, India
ClinicalTrials.gov Identifier: NCT00933790     History of Changes
Other Study ID Numbers: TRC25
First Posted: July 7, 2009    Key Record Dates
Last Update Posted: April 28, 2017
Last Verified: April 2017

Keywords provided by Narendran Gopalan, Tuberculosis Research Centre, India:
TB
HIV
ARR
Short course chemotherapy
Drug resistance

Additional relevant MeSH terms:
HIV Infections
Tuberculosis
Tuberculosis, Pulmonary
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
 Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Rifampin
Pyrazinamide
Ethambutol
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers