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

Tracking Information
First Submitted Date ICMJE	August 29, 2007
First Posted Date ICMJE	August 31, 2007
Last Update Posted Date	July 22, 2011
Study Start Date ICMJE	July 2007
Actual Primary Completion Date	March 2008 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 20, 2011)	Decline in HIV RNA in plasma Rise in CD4 cell count [ Time Frame: Baseline, and Weeks 8, 20 and 32 ]; 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
Original Primary Outcome Measures ICMJE; (submitted: August 29, 2007)	Decline in HIV RNA in plasma Rise in CD4 cell count
Change History	Complete list of historical versions of study NCT00523458 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Study to Determine the Best Dose of Antivirals in Patients With Both TB and HIV
Official Title ICMJE	Not Provided
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.
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	HIV Infections; Tuberculosis
Intervention ICMJE	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)
Study Arms	Active Comparator: 1 Standard dose nevirapine (200 mg 2x daily) in combination with 2 nucleoside analogs Intervention: Drug: efavirenz or nevirapine; Experimental: 2 High dose nevirapine (400 mg in the morning, 200 mg in the evening) in combination with 2 nucleoside analogs Intervention: Drug: efavirenz or nevirapine; Active Comparator: 3 Standard dose efavirenz (600 mg at bedtime) in combination with 2 nucleoside analogs Intervention: Drug: efavirenz or nevirapine; Experimental: 4 High dose efavirenz (800 mg at bedtime) in combination with 2 nucleoside analogs Intervention: Drug: efavirenz or nevirapine
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: July 20, 2011)	5
Original Estimated Enrollment ICMJE; (submitted: August 29, 2007)	240
Actual Study Completion Date	March 2008
Actual Primary Completion Date	March 2008 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Brazil
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00523458
Other Study ID Numbers ICMJE	Stanford Protocol ID: 95564
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Terrence F Blaschke, Principle Investigator, Stanford University School of Medicine
Study Sponsor ICMJE	Stanford University
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Terrence F Blaschke, M.D. Stanford University
PRS Account	Stanford University
Verification Date	July 2011
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP