Bangkok Tenofovir Study
Information source: Centers for Disease Control and Prevention
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Tenofovir (Device)
Phase: Phase 2/Phase 3
Status: Completed
Sponsored by: Centers for Disease Control and Prevention Official(s) and/or principal investigator(s): Kachit Choopanya, MD, Principal Investigator, Affiliation: Bangkok Tenofovir Study Group Michael T Martin, MD, MPH, Study Director, Affiliation: Centers for Disease Control and Prevention Lynn Paxton, MD, Study Director, Affiliation: Centers for Disease Control and Prevention
Summary
The primary goals of this study are to assess the safety and efficacy of daily tenofovir to
prevent parenteral HIV infection among injection drug users (IDUs). Assessment of changes in
HIV associated risk behaviors, adherence to study drug, and, among IDU who become
HIV-infected during the trial, evaluation of HIV viral load set point, CD4 counts, genetic
characterization of infecting HIV viruses, and antiretroviral resistance will also be done.
Clinical Details
Official title: Study of the Safety and Efficacy of Daily Tenofovir to Prevent HIV Infection Among Injection Drug Users in Bangkok, Thailand
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: Adverse eventsrates of HIV seroconversion measured at monthly intervals the frequency of Grade 3 or 4 renal or hepatic function laboratory toxicities or clinical toxicities in blinded tenofovir and placebo arms and which cannot be directly attributed to a cause other than study medications the frequency of adverse clinical events in tenofovir and placebo arms
Secondary outcome: Rates of injecting and needle sharingadherence to study drug/placebo HIV viral load and CD4 counts antiretroviral resistance genetic characteristics of infecting the number of unprotected sexual acts over the course of the trial number of reported sexual partners over the course of the trial proportional use of condoms during sexual intercourse
Detailed description:
This is a phase II/III, randomized, double-blind, placebo-controlled study of the safety and
efficacy of chemoprophylactic tenofovir, administered orally once daily to IDUs. The study
will be conducted in Bangkok at 17 BMA Drug Treatment Clinics. Study participants will be
randomized (1: 1) to receive tenofovir 300 mg or placebo. Participants will be evaluated for
adverse events and HIV seroconversion.
Primary endpoints: The primary efficacy endpoint will be measured by rates of HIV
seroconversion measured at monthly intervals. The primary safety endpoints will be measured
by the frequency of Grade 3 or 4 renal or hepatic function laboratory toxicities or clinical
toxicities in blinded tenofovir and placebo arms, as defined by the Gilead-modified NIAID
Adult Common Toxicity Tables, and which cannot be directly attributed to a cause other than
study medications; and the frequency of adverse clinical events in tenofovir and placebo
arms.
Secondary endpoints: Changes in HIV associated risk behaviors will be measured by rates of
reported injection drug use and injection drug use frequency during the trial; rates of
reported needle sharing; the number of unprotected sexual acts over the course of the trial;
number of reported sexual partners over the course of the trial; and proportional use of
condoms during sexual intercourse.
Medication adherence will be measured as: rates, by interview and documentation on tenofovir
adherence card, of participants taking at least six (86%) of seven daily doses of study drug
each of the four weeks preceding the monthly study visit. Differences in virologic and
immunologic responses to HIV infection among tenofovir and placebo recipients will be
measured by: plasma viral load, measured by quantitative RNA PCR, a predictor of clinical
progression of HIV disease; 14 CD4 cell counts will be measured by flow cytometry. Rates and
nature of HIV antiretroviral genotypic and phenotypic resistance will be measured. Genetic
characteristics of infecting HIV viruses including DNA sequence analysis and antibody
binding studies will be conducted.
In phase II, participants will be followed months 0, 1, 2, 3, then 3 monthly with hematology
and chemistry tests and laboratory evaluations of renal and hepatic function until 200
person-years of observation are accrued. At that point, a DSMB safety assessment will be
conducted. Follow-up of enrolled participants will continue during the DSMB safety
assessment. If safety is confirmed, all phase II participants will continue, and additional
participants will be enrolled into the phase III portion of the trial. Accrual of the target
enrollment of 2,400 IDUs is anticipated to take 48 months.
Participants will choose between two follow-up schedules: monthly (every 4 weeks) or monthly
plus daily with directly observed therapy (DOT). During DOT visits clinic staff will witness
the participant swallow his/her study medication and clinic staff will initial the
participant's tenofovir adherence card. Monthly visits will be the same for both groups and
will include an assessment of tenofovir adherence and adverse events, a pill count and
collection of unused pills, provision of a new 1 month supply of study medication, pre- and
post-test HIV counseling, rapid oral HIV testing, urine pregnancy test (for female
participants), HIV risk reduction counseling, and medication adherence counseling. At 3, 6,
and every 3 months thereafter monthly procedures will be supplemented with a risk behavior
questionnaire.
Eligibility
Minimum age: 20 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Report injection drug use in the 6 months before screening
- Possess a Thai National Identification Card
- Laboratory values as follows within 2 weeks before enrollment:
- HIV oral fluid test non-reactive at screening and pre-enrollment visits
- Hemoglobin 9 gm/dL
- ALT and AST 2. 5 x upper limit of normal (ULN)
- Total bilirubin 1. 5 mg/dL
- Serum amylase 1. 5 x ULN
- Serum phosphorus 2. 2 mg/dL
- No evidence of current or chronic Hepatitis B infection by serology
- Calculated creatinine clearance 60 mL/min by the Cockcroft-Gault formula where
creatinine clearance in mL/min = Male: (140 - age in years) x (wt in kg)/72 x (serum
creatinine in mg/dL) Female:(140 - age in years) x (wt in kg) x 0. 85/72 x (serum
creatinine in mg/dL)
- Willing to abstain from sexual intercourse or use effective contraception during the
trial (oral, injection, or barrier), for women
- Willing and able to provide informed consent for study participation
- Available and committed to DOT or monthly follow-up for at least 12 months
Exclusion Criteria:
- Clinic physicians will determine if a subject with chronic illness requiring
prescription medication can not enroll (medication used for drug treatment is
allowed)
- Positive urine pregnancy test
- Breastfeeding
- History of significant renal, liver, or bone disease
- Any other clinical condition or prior therapy that, in the opinion of the clinic
physician, would make the subject unsuitable for the study or unable to comply with
the dosing requirements
- Concurrent participation in any other HIV prevention trial or drug/vaccine safety
trial. AIDSVAX B/E HIV vaccine trial (CDC protocol #2076) participants and Extension
Study (CDC protocol #3750) participants may be screened for enrollment in the Bangkok
Tenofovir Study.
Locations and Contacts
Thailand Ministry of Public Health - U.S. CDC Collaboration, Nonthaburi 11000, Thailand
Additional Information
Starting date: June 2005
Last updated: February 4, 2015
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