MARCH Vascular Endothelium Substudy (MARCH VE)

Maraviroc Switch Vascular Endothelium (VE) Substudy: a Substudy of MARCH

This is a substudy of MARCH, in which we are exploring the changes in the vascular endothelium using pulse wave tonometry (a non invasive measure of cardiac health) to measure the changes in small and large arterial elasticity in participants of the MARCH study who switch to maraviroc-based regimens over 96 weeks of follow-up.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Drug: NRTI + PI; Drug: maraviroc + PI; Drug: maraviroc + NRTI

Detailed Description

Cardiovascular disease is increasingly recognised as a complication of HIV +/- therapies to treat it. Blood vessel elasticity, or compliance, can be depicted as the ability of the vessels to convert intermittent blood flow (cardiac ejection during systole) to continuous blood flow throughout the cardiac cycle. The compliance, or ability of vessels to accept energy, can be subdivided into elasticity of large and small vessels. Pulse wave tonometry is a non-invasive technique performed using a hand-held tonometer that generates two indices which correspond to large artery elasticity (LAE) and small artery elasticity (SAE). LAE and SAE estimates by pulse waveform analysis have previously shown greater correlation to Framingham risk when directly compared with other techniques such as flow-mediated diltation, and both LAE and SAE are associated with traditional cardiovascular risk factors (smoking, insulin resistance, hypertension).

It is unclear what the net effect of maraviroc, a chemokine-receptor blocker is on cardiovascular function.

The aims of this substudy are:

• To compare changes in the vascular endothelium between the control arm ((N(t)RTI) plus PI/r) and each of the maraviroc switch arms over 48 weeks of follow-up.
• To compare the changes in biomarkers and selected immunological markers between the control arm ((N(t)RTI) plus PI/r) and each of the maraviroc switch arms over 48 weeks of follow-up.

• Study Type: Observational
• Enrollment (Actual): 34

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Italiano de Buenos Aires
  • Buenos Aires, Argentina, C1405CKC
    • Fundacion IDEAA
  • Buenos Aires, Argentina, C1221ADC
    • Hospital General de Agudos "Dr. José María Ramos Mejía"
• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St. Vincent's Hospital
• Germany
  • Frankfurt am Main
    • Frankfurt, Frankfurt am Main, Germany, 60590
      • Johann Wolfgang Goethe-University Hospital, Medical HIVCENTER
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Participants in MARCH

Description

Inclusion Criteria:

• Enrolled prior to treatment in the parent study;
• Provision of written, informed consent for participation in the substudy

Exclusion Criteria:

• Known supraventricular tachycardia such as atrial flutter and/or fibrillation that precludes the measurement of pulse wave using tonometry.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm 1; NRTI and PI	Drug: NRTI + PI; tenofovir zidovudine abacavir lamivudine emtricitabine ritonavir darunavir atazanavir lopinavir fosamprenavir
Arm 2; Maraviroc + PI	Drug: maraviroc + PI; maraviroc ritonavir darunavir atazanavir lopinavir fosamprenavir
Arm 3; maraviroc + NRTI	Drug: maraviroc + NRTI; maraviroc tenofovir zidovudine abacavir lamivudine emtricitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in small arterial elasticity (SAE) as measure by pulse wave tonometry	measured at 6 timepoints week 0, 4, 12, 24, 48, 96	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• Mean change in large arterial elasticity (LAE) as measure by pulse wave tonometry	measured at 6 timepoints, week 0,4,12,24,48,96	96 weeks
• Changes from baseline in selected soluble markers of immune activation, coagulation, vascular and platelet function	stored bloods from the main study will be used to explore changes in vascular biomarkers	96 weeks

Collaborators and Investigators

• Sponsor: Kirby Institute
• Investigators: Principal Investigator: Sarah L Pett, FRACP,FRCPE,PhD, Kirby Institute, UNSW

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: April 25, 2012
• First Submitted That Met QC Criteria: April 25, 2012
• First Posted (ESTIMATE): April 26, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 20, 2016
• Last Update Submitted That Met QC Criteria: January 18, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: cardiovascular function; maraviroc
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: MARCH-Kirby VE substudy