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

Cardiovascular Disease Clinical Trial

Official title:

A Randomized Controlled Trial Comparing Efavirenz With Rilpivirine on Changes in Endothelial Function, Inflammatory Markers, and Oxidative Stress in HIV-uninfected Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01585038
• Other study ID #: TMC278HIV4002
• Status: Completed
• Phase: Phase 4
• First received: April 23, 2012
• Last updated: July 27, 2015
• Start date: July 2012
• Est. completion date: November 2014

Study information

• Verified date: July 2015
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Data and Safety Monitoring Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the cardiovascular profiles of efavirenz and rilpivirine, which are two drugs used to treat HIV infection.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• Efavirenz
600mg orally every evening
• Rilpivirine
25mg orally once daily

Locations

Country	Name	City	State
United States	Indiana Clinical and Translational Sciences Institute	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	Janssen Services, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Flow-mediated Dilation of the Brachial Artery	This is a measure of in vivo endothelial function	Change from baseline to 4 weeks	Yes
Secondary	Inflammatory Markers	Change in high sensitivity C-reactive protein levels	Change from baseline to 4 weeks	Yes
Secondary	Endothelial Activation Markers	Change in soluble vascular cell adhesion molecule-1 levels	Change from baseline to 4 weeks	Yes
Secondary	Oxidative Stress Markers	Change in F2-isoprostane levels	Change from baseline to 4 weeks	Yes