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Efficacy Safety Study Comparing 2 Doses of NVP After Initiating Rifampin-containing TB Therapy

This study has been completed.
Sponsor:
Collaborators:
other sponsors:Japanese MOPH
Labor and Welfare
Thai MOPH
Thai GPO
other collaborators: Bamrasnaradura Infectious Diseases Institute
Chiang Rai Hospital
King Chulalongkorn Memorial Hospital
Central General Chest Institute
The Research Institute of Tuberculosis (Japan)
Information provided by:
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:
NCT00476853
First received: May 20, 2007
Last updated: June 4, 2010
Last verified: June 2010
History of Changes
  Purpose

A 48 week, randomized, open-label, two arm study to compare the efficacy, safety and tolerability of HAART containing nevirapine 400 mg/day versus nevirapine 600 mg/day in HIV-1 infected patients started at 2-6 weeks after initiating rifampicin containing antituberculosis therapy.


Condition Intervention Phase
HIV Infections
Tuberculosis
 Drug: HAART containing nevirapine
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 48 Week, Randomized, Open-label, 2 Arm Study to Compare the Efficacy, Safety and Tolerability of HAART Containing Nevirapine 400mg/Day Versus Nevirapine 600 mg/Day in HIV-1 Infected Patients Started at 2-6 Weeks After Initiating Rifampin Containing Antituberculous Therapy

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures:
  • Efficacy of nevirapine based HAART 400 mg/day versus 600 mg/day on HIV-1 load as measured by HIV-1 RNA quantification in plasma [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety and tolerability of nevirapine based HAART 400 mg/day versus 600 mg/day [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Nevirapine level at week 2, 4 and 12 and 12 hour PK at week 4 (only 20 patients) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Immune recovery syndrome, adherence, clinical improvement, incidence of new/recurrent AIDS events (CDC class C) between two group [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Time to mortality or new/recurrent AIDS events (CDC class C), 1 year mortality rate of TB/HIV patients, emerging of ARV resistant especially nevirapine, emerging of anti-TB resistance [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 42
Study Start Date: October 2005
Study Completion Date: December 2009
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
NVP 400 mg
 Drug: HAART containing nevirapine
Initially NVP 200 mg BID (400 mg per day) was compared to 400 mg BID and 200 mg OD NVP (600 mg per day). 400 mg/day versus 600 mg/day.
Active Comparator: 2
NVP 600 mg
 Drug: HAART containing nevirapine
Initially NVP 200 mg BID (400 mg per day) was compared to 400 mg BID and 200 mg OD NVP (600 mg per day). 400 mg/day versus 600 mg/day.

Detailed Description:

Preliminary data from the HIVNAT PK laboratory indicate that out of 5/60 patients treated with nevirapine (200 mg bid) and rifampicin had sub-therapeutic nevirapine levels (<3.0 mg mg/L). In a control group of 38 patients using nevirapine without rifampicin there were no sub-therapeutic levels. A dose increase of nevirapine while patients who are receiving that rifampicin may be required. Both nevirapine and rifampicin are tepatotoxic agents as are other agents used in treatment of HIV or tuberculosis. Using a higher nevirapine may prevent the occurrence of sub-therapeutic nevirapine levels, but may also induce more liver toxicity. To address these issues, we designed a randomized prospective study to evaluate the safety, efficacy and pharmacokinetics of nevirapine 400 mg/day versus 600 mg/day with a two weeks lead-in 200 mg/day and 400 mg/day respectively, in TB-HIV co-infected patients who taking rifampicin and short-term efficacy and toxicity.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed HIV positive after voluntary counseling and testing
  2. Aged 18-60 years of age
  3. Antiretroviral treatment naïve.
  4. CD4+ cell count of < 200 cells/mm3 at the time of diagnosed TB
  5. TB is diagnosed and using treatment with rifampin base therapy for at least 2 weeks but no longer than 4 weeks duration. The requirement for study entry is at least one acid-fast bacillus (AFB) positive smear with a typical syndrome and/or CXR findings consistent with pulmonary TB. Pulmonary TB and / or extra pulmonary TB will be included if AFB or culture for TB is positive.
  6. No other active OI (CDC class C event)
  7. Negative pregnancy test in females, and willing to use reliable contraception
  8. Able to provide written informed consent.

Exclusion Criteria:

  1. The following laboratory variables, i. absolute neutrophil count (ANC) < 1000 cells/uL ii. hemoglobin < 6.5 g/dL iii. platelet count < 50,000 cells/uL iv. serum AST, ALT > 5 x ULN vi. serum bilirubin > 2 x ULN vii. serum creatinine > 2 x ULN viii. Pregnant or nursing mothers.
  2. Current use of steroid and other immunosuppressive agents.
  3. Current use of any prohibited medications related to compliance and drug pharmacokinetics (see appendix )
  4. Acute therapy for serious infection or other serious medical illness (in the judgment of the site Principal Investigator) requiring systemic treatment and/or hospitalization.
  5. Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the trial.
  6. The persons who had been received a mono-therapy of nevirapine
  7. Unlikely to be able to remain in follow-up for the protocol defined period.
  8. Patients with chronic active liver disease.
  9. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN.
  10. Karnofsky performance score <30%
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00476853

Locations
Thailand
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
Bangkok, Thailand, 10330
Chiangrai Hospital
Chiang Rai, Thailand, 57000
Phan Hospital
Chiang Rai, Thailand, 57000
Mae Chan Hospital
Chiang Rai, Thailand, 57000
Central Chest Hospital
Nonthaburi, Thailand, 11000
Bamrasnaradura Institute
Nonthaburi, Thailand, 11000
Sponsors and Collaborators
The HIV Netherlands Australia Thailand Research Collaboration
other sponsors:Japanese MOPH
Labor and Welfare
Thai MOPH
Thai GPO
other collaborators: Bamrasnaradura Infectious Diseases Institute
Chiang Rai Hospital
King Chulalongkorn Memorial Hospital
Central General Chest Institute
The Research Institute of Tuberculosis (Japan)
Investigators
Principal Investigator: Anchalee Avihingsanon, MD The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
  More Information

Additional Information:
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)  This link exits the ClinicalTrials.gov site

No publications provided by The HIV Netherlands Australia Thailand Research Collaboration

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

Responsible Party: Anchalee Avihingsanon, HIV-NAT
ClinicalTrials.gov Identifier: NCT00476853     History of Changes
Other Study ID Numbers: HIV-NAT 033
Study First Received: May 20, 2007
Last Updated: June 4, 2010
Health Authority: Thailand: Ethical Committee

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:
HIV-TB
nevirapine based HAART with rifampin treated TB
Compare PK profile, efficacy, safety and tolerability of HAART containing nevirapine 400mg/day versus 600 mg/day in HIV/TB co-infected patients
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
 Bacterial Infections
Rifampin
Nevirapine
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on March 03, 2013