Bangkok Tenofovir Study, an HIV Pre-exposure Prophylaxis Trial, Bangkok, Thailand
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| ClinicalTrials.gov Identifier: NCT00119106 |
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Recruitment Status :
Completed
First Posted : July 13, 2005
Results First Posted : January 27, 2021
Last Update Posted : February 10, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infections | Drug: Tenofovir disoproxil Drug: Placebo | Phase 2 Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 2413 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Prevention |
| Official Title: | Study of the Safety and Efficacy of Daily Tenofovir to Prevent HIV Infection Among Injection Drug Users in Bangkok, Thailand |
| Study Start Date : | June 2005 |
| Actual Primary Completion Date : | July 2013 |
| Actual Study Completion Date : | October 2014 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: tenofovir disoproxil fumarate
Participants in the Tenofovir arm will receive daily oral tenofovir
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Drug: Tenofovir disoproxil
Antiretroviral
Other Name: Tenofovir |
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Placebo Comparator: Placebo
Participants in the Placebo are will receive daily oral placebo
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Drug: Placebo
Placebo |
- Rates of HIV Seroconversion [ Time Frame: From date of randomization until the date of first documented seroconversion or date of death from any cause, whichever came first, assessed for an average of 4.0 years, with a maximum duration of 6.9 years ]Kaplan Meier survival curve.
- Renal Toxicity [ Time Frame: Blood tested for creatinine level at enrollment and every 3 months, up to 6.9 years ]Number of Participants with Grade 3 or 4 Renal Laboratory Toxicities
- Adverse Events [ Time Frame: Up to 6.9 years ]Number of Participants with adverse clinical events in tenofovir and placebo arms
- Number of Participants Reporting Injecting and Sharing Needles [ Time Frame: Participants were asked about injecting and needle sharing behaviors at enrollment and every 3 month visit, up to 6.9 years ]
Number of Participants reporting injecting and sharing needles:
Assessed injecting and sharing at baseline and every 3 months during follow-up. We used GEE to determine if there was a significant decline in injecting and sharing.
- Adherence to Study Drug/Placebo [ Time Frame: Participants were asked about adherence at 3 month visits, up to 6.9 years. ]Mean number of days that participants took study drug based on study drug diaries by study group.
- HIV Viral Load Copies/mL Measured at First Positive HIV Test Result by Group [ Time Frame: Among people who seroconverted, viral load was measured at month 1, 2, and every 4 months after HIV seroconversion ]Plasma HIV RNA concentrations.
- Number Participants Who Reported More Than One Sexual Partner at Baseline [ Time Frame: At enrolment ]Number of participants
- Number of Participants With Tenofovir-associated Resistance Mutations. [ Time Frame: Specimens collected at the time of HIV seroconversion ]Measure tenofovir associated resistance mutations (ie, K65R and K70E) in amplified viral RNA specimens from HIV-positive participants in the placebo and tenofovir groups.
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 20 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00119106
| Thailand | |
| Thailand Ministry of Public Health - U.S. CDC Collaboration | |
| Nonthaburi, Thailand, 11000 | |
| Principal Investigator: | Kachit Choopanya, MD | Bangkok Tenofovir Study Group | |
| Study Director: | Michael T Martin, MD, MPH | Centers for Disease Control and Prevention | |
| Study Director: | Lynn Paxton, MD | Centers for Disease Control and Prevention |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Centers for Disease Control and Prevention |
| ClinicalTrials.gov Identifier: | NCT00119106 |
| Other Study ID Numbers: |
CDC-NCHSTP-4370 |
| First Posted: | July 13, 2005 Key Record Dates |
| Results First Posted: | January 27, 2021 |
| Last Update Posted: | February 10, 2021 |
| Last Verified: | February 2015 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Concept sheets are reviewed and approved, modified, or declined by research team. |
| Supporting Materials: |
Study Protocol Informed Consent Form (ICF) |
| Time Frame: | Data available after 2014 |
| Access Criteria: | Concept sheets are reviewed and approved, modified, or declined by research team. |
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HIV Prevention Tenofovir HIV Seronegativity |
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Infection HIV Infections Acquired Immunodeficiency Syndrome 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 Tenofovir Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents |