MARCH Vascular Endothelium Substudy

Completed

• Conditions: Cardiovascular Disease
• Interventions: Drug: NRTI + PI; Drug: maraviroc + NRTI; Drug: maraviroc + PI

• Registration Number: NCT01585753
• Lead Sponsor: Kirby Institute

Brief Summary

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.

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 Timeline

• Study First Submitted: 2012-04-25
• Study First Submitted QC: 2012-04-25
• Study First Posted: 2012-04-26
• Study Start: 2012-06
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-18
• Last Update Posted: 2016-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Arm 1	NRTI + PI	NRTI and PI
Arm 3	maraviroc + NRTI	maraviroc + NRTI
Arm 2	maraviroc + PI	Maraviroc + PI

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (6)

Fundacion IDEAA; 🇦🇷 Buenos Aires, Argentina

Hospital Italiano de Buenos Aires; 🇦🇷 Buenos Aires, Argentina

Johann Wolfgang Goethe-University Hospital, Medical HIVCENTER; 🇩🇪 Frankfurt, Frankfurt am Main, Germany

Hospital General de Agudos "Dr. José María Ramos Mejía"; 🇦🇷 Buenos Aires, Argentina

Chulalongkorn University Hospital; 🇹🇭 Bangkok, Thailand

St. Vincent's Hospital; 🇦🇺 Sydney, New South Wales, Australia