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:
Stanford University
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00523458
First received: August 29, 2007
Last updated: July 20, 2011
Last verified: July 2011
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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:
|
|
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:
|
|
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:
|
|
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:
|
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00523458
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:
|
Tuberculosis Actinomycetales Infections Bacterial Infections Gram-Positive Bacterial Infections Mycobacterium Infections Efavirenz Nevirapine Anti-HIV Agents Anti-Infective Agents |
Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Reverse Transcriptase Inhibitors Therapeutic Uses |
ClinicalTrials.gov processed this record on February 27, 2015