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

May 20, 2007
June 4, 2010
October 2005
September 2008   (final data collection date for primary outcome measure)
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 ]
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 ]
Complete list of historical versions of study NCT00476853 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Safety and tolerability of nevirapine based HAART 400 mg/day versus 600 mg/day [ Time Frame: 48 weeks ]
  • Nevirapine level at week 2, 4 and 12 and 12 hour PK at week 4 (only 20 patients) [ Time Frame: 48 weeks ]
  • Immune recovery syndrome, adherence, clinical improvement, incidence of new/recurrent AIDS events (CDC class C) between two group [ Time Frame: 48 weeks ]
  • 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 ]
Not Provided
Not Provided
 
Efficacy Safety Study Comparing 2 Doses of NVP After Initiating Rifampin-containing TB Therapy
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • Tuberculosis
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: 1
    NVP 400 mg
    Intervention: Drug: HAART containing nevirapine
  • Active Comparator: 2
    NVP 600 mg
    Intervention: Drug: HAART containing nevirapine
Avihingsanon A, Manosuthi W, Kantipong P, Chuchotaworn C, Moolphate S, Sakornjun W, Gorowara M, Yamada N, Yanai H, Mitarai S, Ishikawa N, Cooper DA, Phanuphak P, Burger D, Ruxrungtham K. Pharmacokinetics and 48-week efficacy of nevirapine: 400 mg versus 600 mg per day in HIV-tuberculosis coinfection receiving rifampicin. Antivir Ther. 2008;13(4):529-36.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
42
December 2009
September 2008   (final data collection date for primary outcome measure)

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%
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT00476853
HIV-NAT 033
Yes
Anchalee Avihingsanon, HIV-NAT
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)
Principal Investigator: Anchalee Avihingsanon, MD The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
The HIV Netherlands Australia Thailand Research Collaboration
June 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP