AzTrials
AzTrials

HIV InfectionsPhase 3NCT00625404

FEM-PrEP (Truvada®): Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women

A Phase 3 study testing Truvada in people with HIV Infections, run by FHI 360 at 4 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected… Read more about this study

Who is it for?
Ages 18 to 35 years, women onlyHealthy volunteers can take part
Conditions the study is for
HIV Infections
What is being tested?
Truvada
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
2,120 participants
Where
4 sitesin 3 countries
Study dates
May 2009to Jan 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Willing and able (see criterion 2) to provide written informed consent to be screened for and to participate in the trial
  • Able to answer a percentage of informed consent screening (75%) and enrollment (100%) comprehension quiz questions correctly
  • Between 18-35 years old, inclusive
  • At higher risk of becoming HIV infected
  • Have a final negative result according to the site-specific screening HIV testing algorithm and a final negative result at enrollment according to the study HIV testing algorithm
  • Willing to participate in all aspects of the study and to comply with study procedures, for up to 60 weeks, including:
Show all 26Show fewer
  • Be randomized
  • Use study product as directed
  • Adhere to follow-up schedule and willing to be contacted by site staff between study visits (by phone and/or in person)
  • Use a study-approved effective non-barrier method of contraception for the duration of the study
  • Take study product, as evidenced by swallowing a vitamin tablet that is similar in size to the study product at enrollment
  • Provide contact information and agrees to some form of contact method throughout the study
  • Not intending to relocate out of the area for the duration of the study participation and does not have a job or other obligations that may require long absences from the area ( > 1 month at a time)
  • In general good health and have no condition (social or medical) which, in the opinion of the Site Investigator, would make study participation unsafe or complicate data interpretation
  • Not pregnant or breastfeeding, and does not anticipate a desire for pregnancy during the 52 weeks of on-product participation
  • Medically eligible at screening including:
  • Adequate renal function (serum creatinine ≤ upper limit of normal (ULN) of local range and creatinine clearance ≥ 60ml/min estimated by the Cockcroft-Gault Creatinine Clearance Formula
  • Adequate hepatic function (hepatic transaminases ALT and AST < 2x ULN [according to local normal ranges])
  • HBsAg negative
  • Serum phosphorus levels above the lower limit of the local normal range (according to local normal ranges - grade 3 \& 4 hypophosphatemia will be excluded even if within normal local ranges)
  • Not received or receiving an experimental HIV vaccine, participating in another HIV prevention study or participating in any other clinical trial with a biomedical intervention
  • No clinical signs of liver disease (e.g., ascites, spider angiomata, hepatomegaly, jaundice)
  • No definite evidence of glycosuria or proteinuria (i.e., no repeated positive [ ≥ + 1 ] urine dipstick). If a urine dipstick is positive for either glucose and/or protein at the first test, a second urine sample will be tested.
  • No history of pathological bone fractures
  • No history of adverse reaction to latex
  • Not taking any of the following medications: nephrotoxic agents; aminoglycoside antibiotics (including gentamicin); intravenous (IV) amphotericin B; cidofovir; cisplatin; foscarnet; IV pentamidine; oral or IV vancomycin; oral or IV gancyclovir; other agents with significant nephrotoxic potential; drugs that slow renal excretion; probenecid; immune system modulators; systemic chemotherapeutic agents (i.e. cancer treatment medications); systemic corticosteroids; interleukin-2 (IL-2); immunomodulators; interferon (alpha, beta, or gamma); other antiretrovirals (including nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents)

Who cannot join

None listed.

Trial locations and contacts

4 sites in 3 countries.

4 sites in 3 countries

South Africa2 sites
  • Josha Research Center

    Bloemfontein

  • Setshaba Research Centre

    Pretoria, Gauteng

Other trials in South Africa

Kenya1 site
  • Bondo Clinic, Bondo District Hospital

    Bondo, Nyanza

Other trials in Kenya

Tanzania1 site
  • Arusha Clinic, Levolosi Health Center

    Arusha

Other trials in Tanzania

About this study

Official title: Phase 3, Multi-center, Double-blind, Randomized, Placebo-controlled Effectiveness and Safety Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women

This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected women at risk of becoming infected through sexual intercourse.

The study population included HIV-antibody-negative women between the ages of 18-35 who were at risk of HIV acquisition through sexual intercourse. Each participant was randomized to take either a daily single oral tablet of Truvada®, which is a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg), or an identical placebo.

After enrollment, each participant was followed every four weeks. All participants were followed for an additional eight weeks after study drug was stopped. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.

Read the detailed description

This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected women at risk of becoming infected through sexual intercourse.

The study population included HIV-antibody-negative women between the ages of 18-35 who were at risk of HIV acquisition through sexual intercourse. Each participant was randomized to take either a daily single oral tablet of Truvada®, which is a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg), or an identical placebo. All participants received risk reduction counseling and condoms. Women had to be using a study-approved effective non-barrier contraceptive method at the time of enrollment and were asked to do so for the whole period they were on study drug. They received contraceptive counseling throughout the study. Any diagnosed, treatable sexually transmitted infection was treated free of charge.

After enrollment, each participant was followed every four weeks. All participants were followed for an additional eight weeks after study drug was stopped. Participants at risk for Hepatitis B Virus (HBV) flare were followed every four weeks for 12 weeks after stopping study product. Participants who acquired HIV infection during the study stopped taking the study drug at the time of HIV diagnosis, and will be followed for 52 weeks post diagnosis and were referred for care and treatment. Participants who became pregnant stopped taking the study drug but continued follow-up visits. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.

Conditions
HIV Infections
Being tested
Truvada, Placebo
Keywords
Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), HIV, HIV Prevention, Oral PrEP, Truvada, women, Tenofovir, TDF, FTC, emtricitabine, hepatitis, Pre-exposure Prophylaxis (PrEP), HIV Seronegativity
Medical subject headings
HIV Infections, Hepatitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TruvadaDrug

    Also called TDF/FTC - emtricitabine and tenofovir disoproxil fumarate

    Daily single oral tablet of Truvada - a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg).

  • PlaceboOther

    Daily single oral tablet of Placebo. Tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients.

Study groups in NCT00625404
Study groupRoleWhat they receive
Truvada ArmExperimentalDaily single oral tablet of Truvada (TDF/FTC), a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg).
Receives: Drug: Truvada
Placebo ArmPlacebo comparatorDaily single oral tablet of Placebo. Tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. HIV Infection

    HIV Seroconversion, with time to infection refined based on PCR results obtained from stored specimens.

    Measured: Cumulative HIV infection between enrollment and 52 weeks

  2. Confirmed Grade 2 or Higher Serum Creatinine Toxicity

    Repeat specimens were collected to confirm chemistry toxicities. Grade 2 or higher serum creatinine toxicity was defined as ≥1.4 times the upper limit of normal

    Measured: cumulative toxicity through 52 weeks of product use and 4 weeks post product

  3. Frequency of Adverse Events (AEs) During and Within 4 Weeks After Study Product Administration

    The total number of adverse events in the placebo and Truvada arms during and within 4 weeks after study product administration.

    Measured: 10-26 months per site

  4. Confirmed Grade 3 or Higher Reduction in Phosphorus

    Repeat specimens were collected to confirm chemistry toxicities. Grade 3 phosphorus reduction was defined as ≤2.4mg/dL

    Measured: Through 52 weeks on product and 4 weeks post-product

  5. Confirmed Grade 3 or Higher ALT Elevation

    Grade 3 or higher ALT elevation was defined as ≥ 2.6 times the upper limit of normal

    Measured: Through 52 weeks on product and 4 weeks post-product

  6. Confirmed Grade 3 or Higher AST Elevation

    Grade 3 or higher AST elevation was defined as ≥ 2.6 times the upper limit of normal

    Measured: Through 52 weeks on product and 4 weeks post-product

Secondary outcomes (6)
  1. Plasma HIV RNA Level (HIV-1 Viral Load)

    Viral load at the time of HIV detection, HIV conversion and through 16 weeks

    Measured: up to 16 weeks

  2. CD4+ T-cell Count

    CD4+ T-cell Count at the Time of HIV Seroconversion through 16 weeks

    Measured: Up to 16 weeks

  3. FTC and/or Tenofovir Resistance

    Genotypic resistance to FTC and/or tenofovir at the time of HIV diagnosis and 4 weeks later. If resistance was present, testing was repeated at weeks 12, 24, 36 and 52 as necessary (resistance testing will stop if no resistance is detected).

    participants were classified as having resistance if they had one or more visits in which resistance was detected, even if the resistance became undetectable over time.

    Measured: up to 52 weeks

  4. Pregnancy Complications

    Reported complications during pregnancy, including spontaneous abortion, vaginal or uterine bleeding, emergency c-section and other complications

    Measured: up to 60 weeks

  5. Pill Counts and Participant Report of Adherence to Once-daily Pill Taking

    Pill counts and participant report of adherence to once-daily pill taking reported as mean days study product could have been used according to pill counts

    Measured: Up to 52 weeks

  6. Participant Report of Change in Number of Sexual Partners

    Difference in mean number of reported sexual partners between final study visit and enrollment visit

    Measured: Up to 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2008 (estimated)
  2. Study startMay 2009
  3. Primary completionAug 2012
  4. Study completionJan 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
2,120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00625404
Sponsor's protocol ID
10015
Status last verified
Jun 2018
First submitted
19 Feb 2008
Last updated
26 Jul 2018
Data monitoring committee
Yes

Publications

  • Lut Van Damme, M.D., Amy Corneli, Ph.D. and Douglas Taylor, Ph.D. New England Journal of Medicine 367: 411-422, 2012

  • Mandala J, Nanda K, Wang M, De Baetselier I, Deese J, Lombaard J, Owino F, Malahleha M, Manongi R, Taylor D, Van Damme L. Liver and renal safety of tenofovir disoproxil fumarate in combination with emtricitabine among African women in a pre-exposure prophylaxis trial. BMC Pharmacol Toxicol. 2014 Dec 24;15:77. doi: 10.1186/2050-6511-15-77.

    PubMed 25539648
  • Grant RM, Liegler T, Defechereux P, Kashuba AD, Taylor D, Abdel-Mohsen M, Deese J, Fransen K, De Baetselier I, Crucitti T, Bentley G, Agingu W, Ahmed K, Damme LV. Drug resistance and plasma viral RNA level after ineffective use of oral pre-exposure prophylaxis in women. AIDS. 2015 Jan 28;29(3):331-7. doi: 10.1097/QAD.0000000000000556.

    PubMed 25503265
  • Todd CS, Deese J, Wang M, Hubacher D, Steiner MJ, Otunga S, Van Damme L; FEM-PrEP Study Group. Sino-implant (II)(R) continuation and effect of concomitant tenofovir disoproxil fumarate-emtricitabine use on plasma levonorgestrel concentrations among women in Bondo, Kenya. Contraception. 2015 Mar;91(3):248-52. doi: 10.1016/j.contraception.2014.10.008. Epub 2014 Oct 22.

    PubMed 25459097
  • Van Damme L, Corneli A, Ahmed K, Agot K, Lombaard J, Kapiga S, Malahleha M, Owino F, Manongi R, Onyango J, Temu L, Monedi MC, Mak'Oketch P, Makanda M, Reblin I, Makatu SE, Saylor L, Kiernan H, Kirkendale S, Wong C, Grant R, Kashuba A, Nanda K, Mandala J, Fransen K, Deese J, Crucitti T, Mastro TD, Taylor D; FEM-PrEP Study Group. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012 Aug 2;367(5):411-22. doi: 10.1056/NEJMoa1202614. Epub 2012 Jul 11.

    PubMed 22784040

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Truvada in people with HIV Infections, run by FHI 360 at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in South Africa, Kenya, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

HIV Infection (time frame: Cumulative HIV infection between enrollment and 52 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00625404, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2018.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in