Study protocol

Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial

Alexander M de Vos^1,2 , Annemarieke Rutten² , Hester J van de Zaag-Loonen³ , Michiel L Bots⁴ , Riksta Dikkers³ , Robert A Buiskool⁵ , Willem P Mali² , Daniel D Lubbers³ , Arend Mosterd⁶ , Mathias Prokop² , Benno J Rensing⁷ , Maarten J Cramer¹ , H Wouter van Es⁸ , Frans L Moll⁹ , Eric D van de Pavoordt¹⁰ , Pieter A Doevendans¹ , Birgitta K Velthuis² , Albert J Mackaay¹¹ , Felix Zijlstra¹² and Matthijs Oudkerk³

¹  Department of cardiology, University Medical Center Utrecht, Utrecht, The Netherlands

²  Department of radiology, University Medical Center Utrecht, Utrecht, The Netherlands

³  Department of radiology, University medical Center Groningen, Groningen, The Netherlands

⁴  Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands

⁵  Department of radiology, Meander Medical Center Amerfoort, Amersfoort, The Netherlands

⁶  Department of cardiology, Meander Medical Center Amersfoort, Amersfoort, The Netherlands

⁷  Department of cardiology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands

⁸  Department of radiology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands

⁹  Department of vascular surgery, University Medical Center Utrecht, Utrecht, The Netherlands

¹⁰  Department of vascular surgery, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands

¹¹  Department of vascular surgery, Meander Medical Center Amersfoort, Amersfoort, The Netherlands

¹²  Department of cardiology, University medical Center Groningen, Groningen, The Netherlands

author email corresponding author email

Trials 2008, 9:49doi:10.1186/1745-6215-9-49

Published:	1 August 2008

Abstract

Background

Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms.

Design

The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about 1200 patients are needed to detect a 24% reduction in primary outcome.

Implications

The GROUND study will provide insight into the question whether non-invasive cardiac imaging reduces the risk of cardiovascular events in patients with peripheral arterial disease, but without symptoms of coronary artery disease.

Trial registration

Clinicaltrials.gov NCT00189111