Protocol for the Stimulating β3-Adrenergic Receptors for Peripheral Artery Disease (STAR-PAD) trial: a double-blinded, randomised, placebo-controlled study evaluating the effects of mirabegron on functional performance in patients with peripheral arterial disease

Kristen J Bubb; Jason A Harmer; Meghan Finemore; Sarah Joy Aitken; Zara S Ali; Laurent Billot; Clara Chow; Jonathan Golledge; Rebecca Mister; Michael P Gray; Stuart M Grieve; Naomi Hamburg; Anthony C Keech; Sanjay Patel; Vikram Puttaswamy; Gemma A Figtree

doi:10.1136/bmjopen-2021-049858

Protocol for the Stimulating β₃-Adrenergic Receptors for Peripheral Artery Disease (STAR-PAD) trial: a double-blinded, randomised, placebo-controlled study evaluating the effects of mirabegron on functional performance in patients with peripheral arterial disease

BMJ Open. 2021 Sep 28;11(9):e049858. doi: 10.1136/bmjopen-2021-049858.

Authors

Kristen J Bubb^#^{1

2}, Jason A Harmer^#^{1

3}, Meghan Finemore^#^{1

2}, Sarah Joy Aitken^{1

4}, Zara S Ali^{1

2}, Laurent Billot⁵, Clara Chow^{1

5

6

7}, Jonathan Golledge⁸, Rebecca Mister⁹, Michael P Gray^{1

2}, Stuart M Grieve^{10

11

12}, Naomi Hamburg¹³, Anthony C Keech^{1

9

11}, Sanjay Patel^{1

10

11

12}, Vikram Puttaswamy¹⁴, Gemma A Figtree^{15

2

3}

Affiliations

¹ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
² Kolling Institute of Medical Research, Cardiothoracic and Vascular Health, University of Sydney, St Leonards, New South Wales, Australia.
³ Department of Cardiology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
⁴ Concord Repatriation General Hospital, Concord, New South Wales, Australia.
⁵ The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia.
⁶ Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Westmead, New South Wales, Australia.
⁷ Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia.
⁸ Vascular Biology Unit, James Cook University Queensland Research Centre for Peripheral Vascular Disease, Townsville, Queensland, Australia.
⁹ NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia.
¹⁰ The Heart Research Institute, Newtown, New South Wales, Australia.
¹¹ Charles Perkins Centre, University of Sydney, Camperdown, New South Wales, Australia.
¹² Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
¹³ Boston University, Boston, Massachusetts, USA.
¹⁴ Vascular Surgery, North Shore Private Hospital, Sydney, New South Wales, Australia.
¹⁵ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia gemma.figtree@sydney.edu.au.

^# Contributed equally.

Abstract

Introduction: There is currently only one approved medication effective at improving walking distance in people with intermittent claudication. Preclinical data suggest that the β₃-adrenergic receptor agonist (mirabegron) could be repurposed to treat intermittent claudication associated with peripheral artery disease. The aim of the Stimulating β₃-Adrenergic Receptors for Peripheral Artery Disease (STAR-PAD) trial is to test whether mirabegron improves walking distance in people with intermittent claudication.

Methods and analysis: The STAR-PAD trial is a Phase II, multicentre, double-blind, randomised, placebo-controlled trial of mirabegron versus placebo on walking distance in patients with PAD. A total of 120 patients aged ≥40 years with stable PAD and intermittent claudication will be randomly assigned (1:1 ratio) to receive either mirabegron (50 mg orally once a day) or matched placebo, for 12 weeks. The primary endpoint is change in peak walking distance as assessed by a graded treadmill test. Secondary endpoints will include: (i) initial claudication distance; (ii) average daily step count and total step count and (iii) functional status and quality of life assessment. Mechanistic substudies will examine potential effects of mirabegron on vascular function, including brachial artery flow-mediate dilatation; MRI assessment of lower limb blood flow, tissue perfusion and arterial stiffness and numbers and angiogenesis potential of endothelial progenitor cells. Given that mirabegron is safe and clinically available for alternative purposes, a positive study is positioned to immediately impact patient care.

Ethics and dissemination: The STAR-PAD trial is approved by the Northern Sydney Local Health District Human Research Ethics Committee (HREC/18/HAWKE/50). The study results will be published in peer-reviewed medical or scientific journals and presented at scientific meetings, regardless of the study outcomes.

Trial registration number: ACTRN12619000423112; Results.

Keywords: clinical trials; magnetic resonance imaging; vascular medicine.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Acetanilides
Clinical Trials, Phase II as Topic
Double-Blind Method
Humans
Multicenter Studies as Topic
Peripheral Arterial Disease* / drug therapy
Physical Functional Performance
Quality of Life
Randomized Controlled Trials as Topic
Receptors, Adrenergic, beta-3*
Thiazoles
Walking

Substances

Acetanilides
Receptors, Adrenergic, beta-3
Thiazoles
mirabegron