Back to resultsA Study to Determine the Best Dose of Antivirals in Patients With Both TB and HIV (OPTI-NNRTI)
Primary Purpose
HIV Infections, Tuberculosis
Status
Terminated
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
efavirenz or nevirapine
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections focused on measuring Co-infection, Tuberculosis, HIV, Drug interactions, Non nucleoside reverse transcriptase inhibitors, Therapy, Treatment Naive
Eligibility 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
Sites / Locations
- Hospital Universitario Prof. Edgard Santos/Universidade Federal da Bahia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Experimental
Active Comparator
Experimental
Arm Label
1
2
3
4
Arm Description
Standard dose nevirapine (200 mg 2x daily) in combination with 2 nucleoside analogs
High dose nevirapine (400 mg in the morning, 200 mg in the evening) in combination with 2 nucleoside analogs
Standard dose efavirenz (600 mg at bedtime) in combination with 2 nucleoside analogs
High dose efavirenz (800 mg at bedtime) in combination with 2 nucleoside analogs
Outcomes
Primary Outcome Measures
Decline in HIV RNA in plasma Rise in CD4 cell count
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
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00523458
Brief Title
A Study to Determine the Best Dose of Antivirals in Patients With Both TB and HIV
Acronym
OPTI-NNRTI
Study Type
Interventional
2. Study Status
Record Verification Date
July 2011
Overall Recruitment Status
Terminated
Why Stopped
A delay in protocol approval and approval of laboratory sites in Salvador, Brazil left too little time for completion of enrollment into the study.
Study Start Date
July 2007 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Stanford University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Tuberculosis
Keywords
Co-infection, Tuberculosis, HIV, Drug interactions, Non nucleoside reverse transcriptase inhibitors, Therapy, Treatment Naive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Standard dose nevirapine (200 mg 2x daily) in combination with 2 nucleoside analogs
Arm Title
2
Arm Type
Experimental
Arm Description
High dose nevirapine (400 mg in the morning, 200 mg in the evening) in combination with 2 nucleoside analogs
Arm Title
3
Arm Type
Active Comparator
Arm Description
Standard dose efavirenz (600 mg at bedtime) in combination with 2 nucleoside analogs
Arm Title
4
Arm Type
Experimental
Arm Description
High dose efavirenz (800 mg at bedtime) in combination with 2 nucleoside analogs
Intervention Type
Drug
Intervention Name(s)
efavirenz or nevirapine
Other Intervention Name(s)
Sustiva (efavirenz), Viramune (nevirapine)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Decline in HIV RNA in plasma Rise in CD4 cell count
Description
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
Time Frame
Baseline, and Weeks 8, 20 and 32
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terrence F Blaschke, M.D.
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Universitario Prof. Edgard Santos/Universidade Federal da Bahia
City
Salvador
State/Province
Bahia
ZIP/Postal Code
40110-160
Country
Brazil
12. IPD Sharing Statement
Learn more about this trial
A Study to Determine the Best Dose of Antivirals in Patients With Both TB and HIV
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