Clinical trial NCT06246188: Use of Stress-CMR Using Regadenoson and GE-267 in Adult Patients with Known or Suspected Coronary Artery Disease
Official title: Use of Stress-CMR Using Regadenoson and GE-267 in Adult Patients with Known or Suspected Coronary Artery Disease Using Mobile Cardiac MRI Units in a Single-arm Open-label Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Coronary Artery Disease
Keywords: Cardiac MRI
Stress perfusion cardiac MRI
Regadenoson
GE-267
Diagnosis
Rural Region
mycocardial perfusion defect
mobile MRI
CMR
Cardiac Magnetic Resonance
Lead sponsor: German Heart Institute
Sponsor class: OTHER
Collaborators: name: GE Healthcare
First posted: 2024-02-07
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The population from which the groups or cohorts will be selected are adults with known or suspected coronary artery disease located in Brandenburg or Mecklenburg-Western Pomerania. Either they already participated in the HerzCheck-Trial (NCT05122793) or they are referred from local cardiologists.

Brief summary: Stress cardiac MRI is crucial for diagnosing coronary artery disease in adults. Currently, it is mainly performed with vasodilators in specialized centers. Introducing mobile CMR units could increase accessibility, especially in rural areas, potentially reducing unnecessary invasive procedures. The objectives include demonstrating the feasibility of mobile stress perfusion CMR, detecting CAD using Regadenoson, and evaluating the image quality of GE-267 in real-world scenarios.

Detailed description: Stress-cardiac MRI (CMR) has a Class I indication for the clinical diagnostic workup in adult patients with suspected coronary artery disease (CAD), including those with epicardial as well as microvascular disease (Gulati M et al. 2021; Zeppenfeld et al. 2022). According to large registry data, in more than 90% of stress-CMR-exams the test was performed using a vasodilator (Adenosine/Regadenoson) at tertiary care centers. However, the use of mobile CMR-units would make this high-end diagnostic tool available to much more patients, especially in rural areas, and by this potentially decrease the rate of unnecessary invasive procedures to rule out CAD. Therefore, we define following objectives:

1. Demonstrate the easy performance of stress Perfusion CMR in a mobile setting using a short and patient/user friendly CMR-protocol. Our hypothesis is that there are no differences in performing stress CMR using a mobile setting versus a stationary setting (based on published literature).
2. Detect mycocardial perfusion defect indicating significant CAD using Regadenoson
3. Evaluate the image quality of GE-267 in a real-world setting using a quantitative score-systeme

Eligibility criteria: Inclusion Criteria:

Adults with known or suspected coronary artery disease based one of the following criteria:

1. Abnormal CMR without stress in a previous CMR measurement (e.g. new onset of wall motion abnormalities or reduced LVEF)
2. Referral from local cardiologist based on one of the following criteria:

   1. Patients has a diagnosed coronary artery disease based on other methods
   2. Patients has a high-risk profile based on risk stratification using clinical evaluation (ESC-Score \> 5%), the assessment of LV function by resting echocardiography, and, in the majority of cases, non-invasive assessment of ischaemia or coronary anatomy.
   3. Patients demonstrate chronic kidney disease (CKD III or higher) and diabetes
   4. Patients demonstrate history of peripheral artery disease (PTA/Stent) or TEA of the carotids or previous operation of atherosclerotic aortic aneurysms

      * Male or female subjects aged ≥18 years
      * Patient fully responsible and can understand/sign the study from a legal aspect

Exclusion Criteria:

* Patient refusal to participate
* Any contraindication to perform an MRI exam
* Known Hypersensitivity to the active substance or to any of the excipients in Regadenoson or GE-267
* Any contraindication to aminophylline or theophylline: hypotension, unstable cardiac arrhythmias and acute coronary symptoms
* Unstable angina that has not been stabilized with medical therapy
* Severe hypotension
* Decompensated states of heart failure
* Severe Arrhythmias
* Contraindication to the cardiac MRI examination (e.g. inability to hold breath; severe claustrophobia, metallic devices such as pace makers)
* Second or third degree atrioventricular (AV) block or sinus node dysfunction, unless these patients have a functioning artificial pacemaker
* Known pregnancy or lactation

Primary outcomes:
measure: Detect mycocardial perfusion defect
timeFrame: at baseline
measure: Evaluate the image quality of GE-267
timeFrame: at baseline
Secondary outcomes:
measure: Recommendation of the patient to further procedure
timeFrame: 6-8 months
measure: Comparison of stress-cMRI result and result of invasive diagnostic
timeFrame: 6-8 months
measure: Total examination time
timeFrame: within 2 hours after baseline
measure: Adverse Effects
timeFrame: within 2 hours after baseline
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Deutsches Herzzentrum der Charité
Study officials:
affiliation: Deutsches Herzzentrum der Charité
name: Sebastian Kelle, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nagel E, Klein C, Paetsch I, Hettwer S, Schnackenburg B, Wegscheider K, Fleck E. Magnetic resonance perfusion measurements for the noninvasive detection of coronary artery disease. Circulation. 2003 Jul 29;108(4):432-7. doi: 10.1161/01.CIR.0000080915.35024.A9. Epub 2003 Jul 14.
citation: Hundley WG, Hamilton CA, Thomas MS, Herrington DM, Salido TB, Kitzman DW, Little WC, Link KM. Utility of fast cine magnetic resonance imaging and display for the detection of myocardial ischemia in patients not well suited for second harmonic stress echocardiography. Circulation. 1999 Oct 19;100(16):1697-702. doi: 10.1161/01.cir.100.16.1697.
citation: Kelle S, Roes SD, Klein C, Kokocinski T, de Roos A, Fleck E, Bax JJ, Nagel E. Prognostic value of myocardial infarct size and contractile reserve using magnetic resonance imaging. J Am Coll Cardiol. 2009 Nov 3;54(19):1770-7. doi: 10.1016/j.jacc.2009.07.027.
citation: Tschope C, Ammirati E, Bozkurt B, Caforio ALP, Cooper LT, Felix SB, Hare JM, Heidecker B, Heymans S, Hubner N, Kelle S, Klingel K, Maatz H, Parwani AS, Spillmann F, Starling RC, Tsutsui H, Seferovic P, Van Linthout S. Myocarditis and inflammatory cardiomyopathy: current evidence and future directions. Nat Rev Cardiol. 2021 Mar;18(3):169-193. doi: 10.1038/s41569-020-00435-x. Epub 2020 Oct 12.
citation: Weiss KJ, Nasser SB, Bigvava T, Doltra A, Schnackenburg B, Berger A, Anker MS, Stehning C, Doeblin P, Abdelmeguid M, Talat M, Gebker R, E-Naggar W, Pieske B, Kelle S. Long-term prognostic value of vasodilator stress cardiac magnetic resonance in patients with atrial fibrillation. ESC Heart Fail. 2022 Feb;9(1):110-121. doi: 10.1002/ehf2.13736. Epub 2021 Dec 6.
citation: Sengupta PP, Kramer CM, Narula J, Dilsizian V. The Potential of Clinical Phenotyping of Heart Failure With Imaging Biomarkers for Guiding Therapies: A Focused Update. JACC Cardiovasc Imaging. 2017 Sep;10(9):1056-1071. doi: 10.1016/j.jcmg.2017.07.001.
citation: Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA, Charron P, Corrado D, Dagres N, de Chillou C, Eckardt L, Friede T, Haugaa KH, Hocini M, Lambiase PD, Marijon E, Merino JL, Peichl P, Priori SG, Reichlin T, Schulz-Menger J, Sticherling C, Tzeis S, Verstrael A, Volterrani M; ESC Scientific Document Group. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 Oct 21;43(40):3997-4126. doi: 10.1093/eurheartj/ehac262. No abstract available.
citation: Kramer CM, Barkhausen J, Bucciarelli-Ducci C, Flamm SD, Kim RJ, Nagel E. Standardized cardiovascular magnetic resonance imaging (CMR) protocols: 2020 update. J Cardiovasc Magn Reson. 2020 Feb 24;22(1):17. doi: 10.1186/s12968-020-00607-1.
citation: Pavon AG, Porretta AP, Arangalage D, Domenichini G, Rutz T, Hugelshofer S, Pruvot E, Monney P, Pascale P, Schwitter J. Feasibility of adenosine stress cardiovascular magnetic resonance perfusion imaging in patients with MR-conditional transvenous permanent pacemakers and defibrillators. J Cardiovasc Magn Reson. 2022 Jan 13;24(1):9. doi: 10.1186/s12968-021-00842-0.
citation: Doltra A, Skorin A, Hamdan A, Schnackenburg B, Gebker R, Klein C, Nagel E, Fleck E, Kelle S. Comparison of acquisition time and dose for late gadolinium enhancement imaging at 3.0 T in patients with chronic myocardial infarction using Gd-BOPTA. Eur Radiol. 2014 Sep;24(9):2192-200. doi: 10.1007/s00330-014-3213-y. Epub 2014 May 15.