Trial record 11 of 26 for:    " August 15, 2007":" September 14, 2007"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

A Study to Determine the Best Dose of Antivirals in Patients With Both TB and HIV (OPTI-NNRTI)

This study has been terminated.
(A delay in protocol approval and approval of laboratory sites in Salvador, Brazil left too little time for completion of enrollment into the study.)
Sponsor:
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00523458
First received: August 29, 2007
Last updated: July 20, 2011
Last verified: July 2011
  Purpose

Because drugs used to treat TB can reduce the amount of the anti-HIV drugs that reach the sites where the virus is located, this study is designed to see whether it is necessary to use higher doses of antiviral (anti-HIV) drugs while patients are receiving therapy with rifampin, one of the drugs commonly used to treat TB. Participants will be assigned to one of 4 arms (see below) and will be followed during the time when they are receiving both treatments.


Condition Intervention Phase
HIV Infections
Tuberculosis
Drug: efavirenz or nevirapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Decline in HIV RNA in plasma Rise in CD4 cell count [ Time Frame: Baseline, and Weeks 8, 20 and 32 ] [ Designated as safety issue: No ]
    These laboratory measures would be used to determine if there was a difference in the ARV failure rate between patients receiving standard dose vs high dose treatment with NNRTIs


Enrollment: 5
Study Start Date: July 2007
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Standard dose nevirapine (200 mg 2x daily) in combination with 2 nucleoside analogs
Drug: efavirenz or nevirapine
Patients co-infected with HIV and TB will receive either "standard" doses of nevirapine (200 mg 2x daily) or efavirenz (600 mg daily) or "high" doses of nevirapine (400 mg and 200 mg daily) or efavirenz (800 mg daily) that are chosen to compensate for the change in pharmacokinetics shown to occur when co-infected patients are treated with the antituberculous drug, rifampin.
Other Names:
  • Sustiva (efavirenz)
  • Viramune (nevirapine)
Experimental: 2
High dose nevirapine (400 mg in the morning, 200 mg in the evening) in combination with 2 nucleoside analogs
Drug: efavirenz or nevirapine
Patients co-infected with HIV and TB will receive either "standard" doses of nevirapine (200 mg 2x daily) or efavirenz (600 mg daily) or "high" doses of nevirapine (400 mg and 200 mg daily) or efavirenz (800 mg daily) that are chosen to compensate for the change in pharmacokinetics shown to occur when co-infected patients are treated with the antituberculous drug, rifampin.
Other Names:
  • Sustiva (efavirenz)
  • Viramune (nevirapine)
Active Comparator: 3
Standard dose efavirenz (600 mg at bedtime) in combination with 2 nucleoside analogs
Drug: efavirenz or nevirapine
Patients co-infected with HIV and TB will receive either "standard" doses of nevirapine (200 mg 2x daily) or efavirenz (600 mg daily) or "high" doses of nevirapine (400 mg and 200 mg daily) or efavirenz (800 mg daily) that are chosen to compensate for the change in pharmacokinetics shown to occur when co-infected patients are treated with the antituberculous drug, rifampin.
Other Names:
  • Sustiva (efavirenz)
  • Viramune (nevirapine)
Experimental: 4
High dose efavirenz (800 mg at bedtime) in combination with 2 nucleoside analogs
Drug: efavirenz or nevirapine
Patients co-infected with HIV and TB will receive either "standard" doses of nevirapine (200 mg 2x daily) or efavirenz (600 mg daily) or "high" doses of nevirapine (400 mg and 200 mg daily) or efavirenz (800 mg daily) that are chosen to compensate for the change in pharmacokinetics shown to occur when co-infected patients are treated with the antituberculous drug, rifampin.
Other Names:
  • Sustiva (efavirenz)
  • Viramune (nevirapine)

Detailed Description:

This is an open label, randomized study with 4 arms: 1.) Standard dose and 2.) high dose nevirapine; and 3.) standard dose and 4.) high dose efavirenz. Subjects in all 4 arms will also receive 2 nucleoside analog drugs. Patients will have routine monitoring for the treatment of TB and HIV, as well as some additional blood samples to follow the virus in the blood and to determine the effect of the TB therapy on the amounts of anti-HIV drugs that are in the body.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ARV naïve subjects
  • Documented HIV infection
  • Documented TB infection
  • Platelet count 40,000/mm3
  • Hemoglobin ≥8.0 g/dL
  • Absolute neutrophil count (ANC) >500/mm3
  • AST (SGOT), ALT (SGPT), and alkaline phosphatase <3 X ULN
  • Total bilirubin <2.5 x ULN
  • Calculated creatinine clearance ≥60 mL/min
  • For women of reproductive potential, negative urine pregnancy test

Exclusion Criteria:

  • Unable to provide informed consent.
  • History drug abuse that the investigators suspect will interfere with compliance to study medications and visits.
  • Patients on hemodialysis.
  • Tuberculosis meningitis.
  • Women with CD4 > 250 and men with CD4 > 400 due to higher risk of hepatotoxicity related to use of NVP.
  • Positive serology for hepatitis C.
  • Evidence for active hepatitis B including positive serologies for HBsAg, HBeAg, or HBV-DNA. Note: If anti-HBs is positive, patient is eligible for study if liver enzymes are within the parameters indicated in the inclusion criteria
  • Women who are breast-feeding
  • Known allergy/sensitivity to study drug(s) or their formulations
  • Patients with other OIs or intercurrent illness that could affect their ability to take study drugs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00523458

Locations
Brazil
Hospital Universitario Prof. Edgard Santos/Universidade Federal da Bahia
Salvador, Bahia, Brazil, 40110-160
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Terrence F Blaschke, M.D. Stanford University
  More Information

No publications provided

Responsible Party: Terrence F Blaschke, Principle Investigator, Stanford University School of Medicine
ClinicalTrials.gov Identifier: NCT00523458     History of Changes
Other Study ID Numbers: Stanford Protocol ID: 95564
Study First Received: August 29, 2007
Last Updated: July 20, 2011
Health Authority: United States: Institutional Review Board
United States: Federal Government
Brazil: National Committee of Ethics in Research

Keywords provided by Stanford University:
Co-infection
Tuberculosis
HIV
Drug interactions
Non nucleoside reverse transcriptase inhibitors
Therapy
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
Nevirapine
Efavirenz
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 22, 2014