Effects of Switching Efavirenz to Raltegravir on Vascular Function and Bone Markers in HIV-infected Patients

NCT01270802 | Completed Phase 4 Results DMC

• 1 other identifier: Merck 38258
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV

Keywords

Endothelial function; Vitamin D; Efavirenz; Raltegravir

Outcome Measures

Primary Outcomes (1)

• Change in Flow-mediated Dilation (FMD) of the Brachial Artery

  Change in FMD is a measure of change in endothelial function

  Baseline and 24 weeks

Secondary Outcomes (1)

• Change in Serum Levels of Vitamin D

  Baseline and 24 weeks

Study Arms (2)

Tenofovir/emtricitabine/efavirenz

ACTIVE COMPARATOR

Tenofovir/emtricitabine/efavirenz

Drug: Tenofovir/emtricitabine/efavirenz

Tenofovir/emtricitabine plus raltegravir

EXPERIMENTAL

Tenofovir/emtricitabine/efavirenz is switched to tenofovir/emtricitabine plus raltegravir

Drug: Tenofovir/emtricitabine; Drug: Raltegravir

Interventions

Tenofovir/emtricitabine DRUG

Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine

Also known as: Truvada

Tenofovir/emtricitabine plus raltegravir

Tenofovir/emtricitabine/efavirenz DRUG

Continued therapy with tenofovir/emtricitabine/efavirenz

Also known as: Atripla

Tenofovir/emtricitabine/efavirenz

Raltegravir DRUG

Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine

Also known as: Isentress

Tenofovir/emtricitabine plus raltegravir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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").

You may not qualify if:

• 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).
• Known or suspected malignancy requiring systemic treatment within six months of screening.
• History of ADA-defined diabetes mellitus
• 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.

Sponsors & Collaborators

• Indiana University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Interventions

Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Raltegravir Potassium

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Oxazines; Pyrrolidinones; Pyrrolidines

Limitations and Caveats

The study was open-label. Correction for multiple testing was not performed, so apparently significant results may be falsely positive.

Results Point of Contact

• Title: Dr. Samir K. Gupta, Principal Investigator
• Organization: Indiana University School of Medicine

sgupta1@iu.edu

317-274-7926

Study Officials

• Samir K Gupta, MD, MS

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 4, 2011
• First Posted: January 5, 2011
• Study Start: April 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: April 1, 2013
• Last Updated: December 18, 2013
• Results First Posted: October 24, 2013

Record last verified: 2013-11

Locations

US (1)