HIVPhase 4NCT01270802
Effects of Switching Efavirenz to Raltegravir on Vascular Function and Bone Markers in HIV-infected Patients
A Phase 4 study testing Tenofovir/emtricitabine, Tenofovir/emtricitabine/efavirenz and Raltegravir in people with HIV, run by Indiana University at 1 site in United States.
Trial summary
Efavirenz, a commonly used HIV medication, may cause worsening vascular function and bone problems. The purpose of this study is to determine if switching efavirenz to raltegravir, a newer HIV medication, will improve vascular function and tests of bone health. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- Tenofovir/emtricitabine, Tenofovir/emtricitabine/efavirenz and Raltegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Apr 2013
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection, documented by (1) any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or (2) by two detectable HIV-1 antigens, or (3) two detectable plasma HIV-1 RNA viral loads.
- Age equal to or greater than 18 years.
- Receipt of TDF/FTC/EFV as the subject's initial ART regimen for at least one year prior to Screening.
- Note: Interruptions in TDF/FTC/EFV of up to 10 days total during the 90 days prior to screening are allowed.
- Note: Subjects who had received 3TC (lamivudine) with TDF/EFV as part of their initial regimen but have received TDF/FTC/EFV for at least one year prior to screening will be eligible.
- HIV-1 RNA level <50copies/mL at screening and with a history of having an HIV-1 RNA level of <50copies/mL between 1 and 6 months prior to screening.
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- At least one genotypic resistance test done prior to initiation of TDF/FTC/EFV suggesting no evidence of antiretroviral resistance to any nucleos(t)ide reverse transcriptase inhibitor or non-nucleoside reverse transcriptase inhibitor.
- No previous use of raltegravir or other integrase inhibitor.
- For women of reproductive potential, a negative urine pregnancy test at screening and willingness to use two forms of birth control during the course of the study. Acceptable forms of birth control include condoms (with or without a gel that can kill sperm), a diaphragm or cervical cap (with or without a gel that can kill sperm), an intrauterine device (IUD), or hormonal-based birth control ("the pill").
Who cannot join
- Inability to complete written, informed consent.
- Incarceration at the time of any study visit.
- Diagnosed vascular disease (history of angina pectoris, coronary disease, peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise known atherosclerotic disease).
- Diagnosed disease or process, besides HIV infection, associated with increased systemic inflammation (including, but not limited to, systemic lupus erythematosis, inflammatory bowel diseases, other collagen vascular diseases).
- Note: Hepatitis B or C co-infections are NOT exclusionary
- Known or suspected malignancy requiring systemic treatment within six months of screening.
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- History of ADA-defined diabetes mellitus
- Note: History of gestational diabetes is not exclusionary if the potential subject does not have current ADA-defined diabetes.
- History of migraine headaches.
- History of Raynaud's phenomenon.
- History of cardiac arrhythmias or cardiomyopathy.
- Uncontrolled hyperthyroidism or hypothyroidism, defined as TSH values outside of the local reference range on most recent clinical assessment.
- History of hypoparathyroidism or hyperparathyroidism, even if treated.
- Known allergy or intolerance to nitroglycerin.
- History of carotid bruits.
- Creatinine clearance < 50mL/min (using the Cockcroft-Gault equation) using a serum creatinine level measured at screening.
- Hemoglobin < 9.0mg/dL at screening.
- Alanine aminotransferase (ALT) level or aspartate aminotransferase (AST) > 3 times ULN at screening.
- Total bilirubin > 2.5 times ULN at screening.
- Fever, defined as T ≥ 38.0C within 48 hours prior to screening.
- Note: Fever within 48 hours prior to each main study visit will require postponement of that study visit until the patient has defervesced (T < 38.0C) for at least 48 hours; fevers continuing past the allowed study visit timeframe will result in study discontinuation.
- Therapy for acute infection or other serious medical illnesses within 14 days prior to screening.
- Note: Therapy for acute infection or other serious medical illnesses that overlaps with a main study visit will result in postponement of that study visit until the course of therapy is completed; postponement outside of the allowed study visit timeframe will result in study discontinuation.
- Pregnancy or breastfeeding during the course of the study.
- Hypotension, defined as systolic blood pressure < 90mmHg, at time of screening.
- Note: Hypotension noted prior to brachial artery reactivity testing on each main study visit will result in study visit postponement of at least one day until systolic pressure is ≥ 90mmHg the morning of brachial reactivity testing; postponement outside of the allowed study visit timeframe will result in study discontinuation.
- Uncontrolled hypertension, defined as systolic blood pressure > 160mmHg or diastolic blood pressure > 100mgHg at screening.
- Receipt of investigational agents, cytotoxic chemotherapy, systemic glucocorticoids (of any dose), or anabolic steroids at screening.
- Note: Physiologic testosterone replacement therapy is not exclusionary.
- Receipt of lipid-lowering drugs or anticonvulsants (defined as those drugs with significant CYP 450 induction or inhibition) screening.
- Use of sildenafil, vardenafil, or tadalafil within 72 hours (before or after) of each main study visit.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University School of Medicine
Indianapolis, Indiana, 46202
About this study
Official title: A Randomized Controlled Pilot Trial Comparing Continued Antiretroviral Therapy With Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV) With Switch to Tenofovir/Emtricitabine/Raltegravir (TDF/FTC/RAL) on Changes in Endothelial Function and Markers of Bone Metabolism
Efavirenz, a commonly used HIV medication, may cause worsening vascular function and bone problems. The purpose of this study is to determine if switching efavirenz to raltegravir, a newer HIV medication, will improve vascular function and tests of bone health.
Read the detailed description
Cardiovascular disease (CVD) is an increasingly important comorbidity in HIV-infected patients. Our preliminary data suggests that efavirenz may worsen endothelial function, which in turn may increase the risk for future CVD events. Efavirenz has also been linked to lower vitamin D levels, which may in turn result in increased bone fragility. Raltegravir is not known to affect either endothelial function or vitamin D levels. Therefore, switching efavirenz to raltegravir in patients with suppressed HIV viremia may lead to improved outcomes.
- Conditions
- HIV
- Being tested
- Tenofovir/emtricitabine, Tenofovir/emtricitabine/efavirenz, Raltegravir
- Keywords
- Endothelial function, Vitamin D, Efavirenz, Raltegravir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir/emtricitabineDrug
Also called Truvada
Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine
Tenofovir/emtricitabine/efavirenzDrug
Also called Atripla
Continued therapy with tenofovir/emtricitabine/efavirenz
RaltegravirDrug
Also called Isentress
Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir/emtricitabine/efavirenz | Active comparator | Tenofovir/emtricitabine/efavirenz Receives: Drug: Tenofovir/emtricitabine/efavirenz |
| Tenofovir/emtricitabine plus raltegravir | Experimental | Tenofovir/emtricitabine/efavirenz is switched to tenofovir/emtricitabine plus raltegravir Receives: Drug: Tenofovir/emtricitabine; Drug: Raltegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Flow-mediated Dilation (FMD) of the Brachial Artery
Change in FMD is a measure of change in endothelial function
Measured: Baseline and 24 weeks
Secondary outcomes (1)
Change in Serum Levels of Vitamin D
Change in serum levels of 24-OH-vitamin D provide a measure of the amount of change in vitamin D in the body
Measured: Baseline and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2011 (estimated)
- Study startApr 2011
- Primary completionOct 2012
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Samir Gupta, Indiana University
- Investigators
- Samir K Gupta, MD, MS, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01270802
- Sponsor's protocol ID
- Merck 38258
- Status last verified
- Nov 2013
- First submitted
- 4 Jan 2011
- Last updated
- 18 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Pilot Trial Comparing Continued Antiretroviral Therapy With Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV) With Switch to Tenofovir/Emtricitabine/Raltegravir (TDF/FTC/RAL) on Changes in Endothelial Function and Markers of Bone Metabolism
- ClinicalTrials.gov ID
- NCT01270802
- Acronym / sponsor ID
- Merck 38258
- Conditions
- HIV
- Keywords
- Endothelial function, Vitamin D, Efavirenz, Raltegravir
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Apr 2011
- Primary completion
- Oct 2012 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 5 Jan 2011 (estimated)
- Results
- Posted 24 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Efavirenz, a commonly used HIV medication, may cause worsening vascular function and bone problems. The purpose of this study is to determine if switching efavirenz to raltegravir, a newer HIV medication, will improve vascular function and tests of bone health.
Detailed description
Cardiovascular disease (CVD) is an increasingly important comorbidity in HIV-infected patients. Our preliminary data suggests that efavirenz may worsen endothelial function, which in turn may increase the risk for future CVD events. Efavirenz has also been linked to lower vitamin D levels, which may in turn result in increased bone fragility. Raltegravir is not known to affect either endothelial function or vitamin D levels. Therefore, switching efavirenz to raltegravir in patients with suppressed HIV viremia may lead to improved outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir/emtricitabine/efavirenz | Active comparator | Drug: Tenofovir/emtricitabine/efavirenzTenofovir/emtricitabine/efavirenz |
| Tenofovir/emtricitabine plus raltegravir | Experimental | Drug: Tenofovir/emtricitabine, Drug: RaltegravirTenofovir/emtricitabine/efavirenz is switched to tenofovir/emtricitabine plus raltegravir |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- HIV-1 infection, documented by (1) any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or (2) by two detectable HIV-1 antigens, or (3) two detectable plasma HIV-1 RNA viral loads.
- Age equal to or greater than 18 years.
- Receipt of TDF/FTC/EFV as the subject's initial ART regimen for at least one year prior to Screening.
- Note: Interruptions in TDF/FTC/EFV of up to 10 days total during the 90 days prior to screening are allowed.
- Note: Subjects who had received 3TC (lamivudine) with TDF/EFV as part of their initial regimen but have received TDF/FTC/EFV for at least one year prior to screening will be eligible.
Key exclusion criteria (32 listed)
- Inability to complete written, informed consent.
- Incarceration at the time of any study visit.
- Diagnosed vascular disease (history of angina pectoris, coronary disease, peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise known atherosclerotic disease).
- Diagnosed disease or process, besides HIV infection, associated with increased systemic inflammation (including, but not limited to, systemic lupus erythematosis, inflammatory bowel diseases, other collagen vascular diseases).
- Note: Hepatitis B or C co-infections are NOT exclusionary
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir/emtricitabineAlso: TruvadaEfavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine | Drug | Tenofovir/emtricitabine plus raltegravir |
| Tenofovir/emtricitabine/efavirenzAlso: AtriplaContinued therapy with tenofovir/emtricitabine/efavirenz | Drug | Tenofovir/emtricitabine/efavirenz |
| RaltegravirAlso: IsentressEfavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine | Drug | Tenofovir/emtricitabine plus raltegravir |
Primary outcome
Change in Flow-mediated Dilation (FMD) of the Brachial Artery
Time frame: Baseline and 24 weeks
Change in FMD is a measure of change in endothelial function
1 secondary outcome
Change in Serum Levels of Vitamin D
Time frame: Baseline and 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samir K Gupta, MD, MS principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tenofovir/emtricitabine, Tenofovir/emtricitabine/efavirenz and Raltegravir in people with HIV, run by Indiana University at 1 site in United States.
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 9 inclusion and 32 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 18 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 24 Oct 2013). 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?
Change in Flow-mediated Dilation (FMD) of the Brachial Artery (time frame: Baseline and 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Dec 2013; AzTrials last refreshed its copy on 7 Nov 2026.