Efavirenz Versus Rilpivirine on Vascular Function, Inflammation, and Oxidative Stress

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01585038
Recruitment Status : Completed
First Posted : April 25, 2012
Results First Posted : July 2, 2015
Last Update Posted : August 14, 2015
Janssen Services, LLC
Information provided by (Responsible Party):
Samir K Gupta, MD, MS, Indiana University

April 23, 2012
April 25, 2012
June 11, 2015
July 2, 2015
August 14, 2015
July 2012
May 2014   (Final data collection date for primary outcome measure)
Change in Flow-mediated Dilation of the Brachial Artery [ Time Frame: Change from baseline to 4 weeks ]
This is a measure of in vivo endothelial function
Flow-mediated dilation of the brachial artery [ Time Frame: 4 weeks ]
This is a measure of in vivo endothelial function
Complete list of historical versions of study NCT01585038 on Archive Site
  • Inflammatory Markers [ Time Frame: Change from baseline to 4 weeks ]
    Change in high sensitivity C-reactive protein levels
  • Endothelial Activation Markers [ Time Frame: Change from baseline to 4 weeks ]
    Change in soluble vascular cell adhesion molecule-1 levels
  • Oxidative Stress Markers [ Time Frame: Change from baseline to 4 weeks ]
    Change in F2-isoprostane levels
  • Inflammatory Markers [ Time Frame: 4 weeks ]
    hsCRP, IL-6, sTNFRI, sTNFRII
  • Endothelial Activation Markers [ Time Frame: 4 weeks ]
    sVCAM-1, sICAM-1, vWF, IP-10
  • Oxidative Stress Markers [ Time Frame: 4 weeks ]
  • Metabolic markers [ Time Frame: 4 weeks ]
    HOMA-IR, fasting lipid profile
Not Provided
Not Provided
Efavirenz Versus Rilpivirine on Vascular Function, Inflammation, and Oxidative Stress
A Randomized Controlled Trial Comparing Efavirenz With Rilpivirine on Changes in Endothelial Function, Inflammatory Markers, and Oxidative Stress in HIV-uninfected Healthy Volunteers
The purpose of this study is to compare the cardiovascular profiles of efavirenz and rilpivirine, which are two drugs used to treat HIV infection.
This is a randomized, controlled, open-label, single-center study comparing the effects of efavirenz (EFV) versus rilpivirine (RPV) on endothelial function in a total of 40 HIV-uninfected healthy volunteers (20 in each arm) at the Indiana University Medical Center. Enrolled subjects will have their brachial artery flow-mediated dilation (FMD), a measure of endothelial function, and other cardiovascular, inflammatory, and oxidative stress parameters measured at baseline and again after 4 weeks of study treatment.
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Cardiovascular Disease
  • Drug: Efavirenz
    600mg orally every evening
    Other Name: Sustiva, Stocrin
  • Drug: Rilpivirine
    25mg orally once daily
    Other Name: Edurant
  • Active Comparator: Efavirenz
    Efavirenz 600mg given nightly without food for 30 days
    Intervention: Drug: Efavirenz
  • Active Comparator: Rilpivirine
    Rilpivirine 25mg given daily with meals for 30 days
    Intervention: Drug: Rilpivirine
Gupta SK, Slaven JE, Kamendulis LM, Liu Z. A randomized, controlled trial of the effect of rilpivirine versus efavirenz on cardiovascular risk in healthy volunteers. J Antimicrob Chemother. 2015 Oct;70(10):2889-93. doi: 10.1093/jac/dkv195. Epub 2015 Jul 13.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
November 2014
May 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. 18 years of age or older
  2. Negative ELISA for HIV-1 or HIV-2 at screening
  3. Negative hepatitis B surface antigen at screening
  4. Negative hepatitis C antibody at screening
  5. 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
  6. For men who are capable of impregnating a female sexual partner, a willingness to use condoms with spermicidal gel for all sexual contacts during the course of the study
  7. No documented history of or receipt of medications being used to treat any psychiatric disorder, including (but not limited to) depression, dysthymia, mania, bipolar disease, schizophrenia, or previous suicidal ideation/attempts
  8. No anticipated changes or additions to other medical therapies during the course of the study
  9. No documented history of seizure disorder

Exclusion Criteria:

  1. Inability to provide written, informed consent
  2. Known allergy/intolerance to rilpivirine, efavirenz, or nitroglycerin
  3. Absolute neutrophil count < 750cell/mL at screening
  4. Hemoglobin < 11g/dL at screening
  5. Platelet count < 100,000/mL at screening
  6. Estimated creatinine clearance (per Cockcroft-Gault equation) < 55 mL/min at screening
  7. Liver transaminases (AST or ALT) > 100 IU/mL or total bilirubin > 1.5mg/dL at screening
  8. Serum glucose > 200mg/dL at screening
  9. Serum total cholesterol > 190mg/dL at screening
  10. Breastfeeding at screening or during the course of the study
  11. Hypotension, defined as SBP < 90mmHg at time of each main study visit before brachial artery ultrasound measurements
  12. Hypertension, defined as SBP > 160mmHg at time of screening
  13. Receipt of investigational agents within 30 days of each screening visit or anticipated use during the trial
  14. Receipt of cytotoxic chemotherapy within 30 days of each screening visit or anticipated use during the trial
  15. Receipt of systemic glucocorticoids (> 10mg/day of prednisone or the equivalent), inhaled/nasal/topical fluticasone, or anabolic steroids within 30 days of each screening visit or anticipated use during the trial
  16. Use of sildenafil (Viagra or Silagra), vardenafil (Levitra), or tadalafil (Cialis), within 72 hours (before or after) of brachial artery reactivity testing
  17. Indwelling vascular catheters within any upper body vessel at time of brachial artery reactivity testing
  18. Active drug or alcohol use or dependence that, in the opinion of the investigator or study personnel, would interfere with adherence to study requirements
  19. Acute therapy for serious infection or other serious medical illnesses (in the judgment of the site investigator) requiring systemic treatment and/or hospitalization within 14 days prior to each screening and study visit
  20. History of migraine headaches
  21. History of Raynaud's phenomenon
  22. History of cardiac arrythmias
  23. History of hypothyroidism or hyperthyroidism that is untreated (defined as a TSH outside the normal range on most recent testing during normal clinical care)
  24. History of carotid bruits
  25. History of any tobacco use (cigarette smoking, cigar smoking, chewing tobacco) or nicotine replacement treatments (patch, gum) within 45 days of screening
  26. Drugs/therapies with significant CYP 450 induction or inhibition potential at screening
  27. Use of antacids, H2-blockers, or proton pump inhibitors within 30 days of screening or anticipated use of these drugs during the trial
  28. Any history of injection or illicit drug use
  29. Presence of fever, defined as an oral or tympanic temperature > 100.3F, at either the Entry or Closeout Visits
  30. On the PHQ-9 depression questionnaire at screening, a total score of more than 9 or any score over 0 on question 9.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
Samir K Gupta, MD, MS, Indiana University
Indiana University
Janssen Services, LLC
Principal Investigator: Samir K Gupta, MD, MS Indiana University School of Medicine
Indiana University
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP