Eur Radiol (2017) 27:821–830 DOI 10.1007/s00330-016-4437-9 CONTRAST MEDIA Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial Stephan Achenbach1 & Jean-François Paul2 & François Laurent3,4 & Hans-Christoph Becker5 & Marco Rengo6 & Jerome Caudron7 & Sebastian Leschka8 & Olivier Vignaux9 & Gesine Knobloch10 & Giorgio Benea11 & Thomas Schlosser12 & Jordi Andreu13 & Beatriz Cabeza14 & Alexis Jacquier15 & Miguel Souto16 & Didier Revel17 & Salah Dine Qanadli18 & Filippo Cademartiri19 & on behalf of the X-ACT Study Group Received: 7 August 2015 /Revised: 19 May 2016 /Accepted: 23 May 2016 /Published online: 7 June 2016 # The Author(s) 2016. This article is published with open access at Springerlink.com Abstract attenuation, signal and contrast to noise ratio (SNR, CNR). Objectives To demonstrate non-inferiority of iobitridol 350 Patients were considered evaluable if no segment had a for coronary CT angiography (CTA) compared to higher score of 0. iodine content contrast media regarding rate of patients Results Per-patient, the rate of fully evaluable CT scans evaluable for the presence of coronary artery stenoses. was 92.1, 95.4 and 94.6 % for iobitridol, iopromide and Methods In this multicentre trial, 452 patients were randomized iomeprol, respectively. Non-inferiority of iobitridol over to receive iobitridol 350, iopromide 370 or iomeprol 400 and the best comparator was demonstrated with a 95 % CI underwent coronary CTA using CT systems with 64- of the difference of [-8.8 to 2.1], with a pre-specified detector rows or more. Two core lab readers assessed 18 non-inferiority margin of -10 %. Although average at- coronary segments per patient regarding image quality tenuation increased with higher iodine concentrations, (score 0 = non diagnostic to 4 = excellent quality), vascular average SNR and CNR did not differ between groups. * Stephan Achenbach 8 Department of Radiology, Saint Gallen Hospital, Saint [email protected] Gallen, Switzerland on behalf of the X-ACT Study Group 9 Department of Radiology, Cochin Hospital, Paris, France 10 Department of Radiology, La Charité, Berlin, Germany 1 Department of Cardiology, Friedrich-Alexander-Universität 11 Ospedale del Delta, Ferrara, Italy Erlangen-Nürnberg, Ulmenweg 18, 91054 Erlangen, Germany 12 2 Department of Radiology, Centre Chirurgical Marie Lannelongue, Le Elisabeth-Krankenhaus Hospital, Essen, Gerrmany Plessis Robinson, France 13 Hospital Vall d’Hebron, Barcelona, Spain 3 University of Bordeaux, Centre de Recherche Cardio-Thoracique de 14 Hospital Clinico San Carlos, Madrid, Spain Bordeaux, U1045, F-33000 Bordeaux, France 15 Department of Radiology, La Timone Adult Hospital, 4 ’ CHU de Bordeaux, Service d Imagerie Thoracique et Marseille, France Cardiovasculaire, F-33600 Pessac, France 16 Complejo Hospitalario Universitario, Santiago de Compostela, Spain 5 Department of Clinical Radiology, University Hospital Grosshadern, Munich, Germany 17 Department of Radiology, Louis Pradel Hospital, Lyon, France 6 Department of Radiological Sciences, Oncology and Pathology, 18 Department of Radiology, University of Lausanne, Sapienza – University of Rome, ICOT Hospital, Latina, Italy Lausanne, Switzerland 7 Department of Radiology, University Hospital of Rouen, 19 Department of Radiology, Giovanni XXIII Hospital, Monastier di Rouen, France Treviso, Italy 822 Eur Radiol (2017) 27:821–830 Conclusions With current CT technology, iobitridol 350 mg inferiority of iobitridol 350 compared to the best of the two iodine/ml is not inferior to contrast media with higher iodine comparators in terms of image quality and interpretability as concentrations in terms of image quality for coronary stenosis measured by the rate of patients with CT scans evaluable for the assessment. identification of coronary artery stenosis. Key Points • Iodine concentration is an important parameter for image quality in coronary CTA. Material and methods • Contrast enhancement must be balanced against the amount of iodine injected. Study design and patient enrolment conditions • Iobitridol 350 is non-inferior compared to CM with higher iodine concentrations. This study was a non-inferiority, multicentre, randomized, • Higher attenuation with higher iodine concentrations, but no double-blind, clinical trial on three parallel groups. Patients SNR or CNR differences. were included in 23 centres from five countries between November 2010 and September 2012 and randomized on a Keywords Coronary computed tomography angiography . 1:1:1 ratio to undergo clinically indicated coronary CTA after Image quality . Contrast media . Iodine concentration . Safety injection of iobitridol, iopromide or iomeprol. The study was approved by each local ethics committees and the National Health Authorities. Written informed consent was obtained Introduction from each participating patient. Symptomatic adult patients with suspected coronary artery Coronary computed tomography angiography (coronary disease (CAD), and scheduled for coronary CT angiography CTA) has become widely accepted in clinical practice [1–3]. were enrolled in this study. Patients could not be included if Technology progress has increased the robustness and diag- they had both a contraindication to β-blocker medications and a nostic performance of coronary CTA, resulting in improved baseline heart rate above 65 beats per minute (bpm). Additional image quality and lower radiation exposure [4–9]. reasons for exclusion were the presence of arrhythmias or non- The protocols for administration of intravenous contrast me- sinus rhythm, coronary artery bypass grafts or stents, artificial dia (CM) are of major importance in coronary CTA, usually heart valves, moderate to severe aortic valve stenosis, hyperthy- performed to identify coronary artery stenoses but also calcified roidism, clinical instability, severe renal failure or previous in- and non-calcified plaques [10–13]. The optimal intravascular jection of any CM within 48 hours prior to the study. attenuation for coronary CT angiography is under debate [14, 15]. Several publications suggested that adequate opacification Patient preparation of the vessel lumen for the simultaneous identification of both calcified and non-calcified plaques requires a careful contrast β-blockers were mandatory if heart rate was >65 bpm. The injection protocol that achieves a lumen opacification of at least specific drug, dose and mode of administration were selected 300 HU [15–17]. In principle, the Iodine Delivery Rate (IDR) according to site routine practice. A minimum dose of 0.8 mg should be the reference when using different compounds for of sublingual nitroglycerine spray was mandatory immediate- intraluminal enhancement [18]. However, most centres do not ly before the CT examination. Other pre-medication was per- use this approach in clinical practice. mitted, given according to operator preference, and recorded. Higher iodine concentration of the injected CM is associated with higher attenuation [16, 19]. However, increasing the total Injection of contrast media amount of iodine injected could raise safety issues for patients at risk such as contrast induced nephropathy [20–22]. For each patient, one of three CM was delivered intravenous- Therefore, adequate contrast enhancement must be balanced ly: Iobitridol 350 mg iodine/ml (Xenetix®, Guerbet, Aulnay- against the amount of iodine injected. Several studies have ad- sous-Bois, France), iopromide 370 mg/ml (Ultravist®, Bayer dressed the level of attenuation with different CM [14, 23, 24], Healthcare, Berlin, Germany) and iomeprol 400 mg/ml but few studies evaluated the impact of their concentration on (Iomeron®, Bracco, Milan, Italy). Delivered volume and de- image quality [25]. Furthermore, whether differences less than livery rate of CM was consistent for the three CM but varied 50 mg/ml of iodine concentration could affect image quality according to patient body weight (BW): 60 ml injected at remains to be clarified. The present study compared a CM with 4 ml/s for a BW <60 kg, 75 ml at 5 ml/s for a BW between iodine concentration of 350 mg iodine/ml (iobitridol) to two 60 and 80 kg, 90 ml at 6 ml/s for a BW >80 kg. Therefore, the CM with higher iodine concentrations (iopromide 370 mg/ml iodine-delivery rate was lowest for iobitridol. CM was and iomeprol 400 mg/ml) for coronary CTA. The main objec- warmed and injections were followed by a 100 % saline flush tive of the study was to demonstrate the statistical non- of 75 ml administered at the same rate as the CM. Eur Radiol (2017) 27:821–830 823 Scan protocol Society of Cardiovascular Computed Tomography (SCCT) cor- onary segmentation model [29] (4 = excellent quality, full con- All coronary CTAs were performed on systems with at least 64 fidence without any doubts concerning the presence/absence of detector rows (single or dual source). The tube voltage was luminal stenosis; 3 = good quality, confidence concerning the adapted to the patient’s BW depending on the equipment used presence/absence of luminal stenosis; 2 = moderate quality, rel- in the site: either 120 kVp for all patients or 120 kVp for BW ative confidence, with minor doubts concerning the presence/ ≥80 kg and 100 kVp for BW <80 kg. Each patient first received absence of luminal stenosis; 1 = poor quality, some doubts a non-contrast acquisition for the quantification of coronary concerning the presence/absence