Clinical trial NCT06237673: The "CAD-Man" EXTEND Study
Official title: A Randomized, Controlled Trial in Patients With Suspected Coronary Artery Disease Based on Acute or Chronic Atypical Angina Pectoris - EXTEND
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Coronary Artery Disease
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2024-02-01
Enrollment: 318
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: CAD-Man Extend is the long-term follow-up (clinical, laboratory, and computed tomography (CT) imaging) of a single-center, randomized, controlled CAD-Man trial comparing a CT-first strategy with a direct- invasive coronary angiography (ICA) diagnostic and management strategy, in 329 patients clinically referred for ICA with atypical angina or chest pain.

Overall goal:

The extension of CAD-Man follow-up (clinical, laboratory, and CT imaging) to approximately 10 years will provide the opportunity to compare plaque burden with CT-guided management versus direct-ICA at long-term and other endpoints.

Detailed description: The CAD-Man (Coronary Artery Disease Management with Multislice Computed Tomography and Magnetic Resonance Imaging in Patients with Atypical Angina Pectoris) trial evaluated whether computed tomography (CT) or invasive coronary angiography (ICA) should be performed in patients clinically referred for coronary angiography with an intermediate probability of coronary artery disease. Patients with suspected CAD were randomized 1:1 ratio to CT, followed by ICA if positive for obstructive CAD, or to direct ICA. In both tests, obstructive CAD was defined as at least a 50% diameter stenosis in the left main coronary artery or at least a 70% diameter stenosis in other coronary arteries. Investigators and participants were blinded to randomization sequence but could not be blinded to the assigned group because of the apparent differences between CT and ICA. Independent investigators, who were blinded to the randomization group and were not part of the study team, anonymously assessed outcomes. Results on the comparative effectiveness of CT and ICA in preventing the primary outcome of major procedural complications within 48 hours of the last procedure and major adverse events (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) were published for a median follow-up of 3.3 years.

The primary results and additional subgroup analyses of the CAD-Man trial led to three new hypotheses that will be evaluated in the CAD-Man Extend study.

1. Main hypothesis:

   Whether CT-guided management of patients with atypical angina results in a reduction in coronary plaque burden (as determined by repeat CT scan) compared with direct-ICA management until 10 years.
2. Secondary hypothesis:

1. Whether clinical characteristics or blood levels and lipid-lowering medications have an impact on intraindividual progression of coronary plaques in patients in the CT group.

2. Whether primary CT examination in patients with atypical angina leads to a reduction in chronic impairment of renal function after 10-years compared with initial ICA examination.

Eligibility criteria: Inclusion Criteria:

* Patients with suspected CAD
* Patients with atypical angina
* Patients who have previously participated in the CAD-Man study and have not died at a median follow-up of 3.3 years.

Exclusion Criteria:

Exclusion criteria for additional CT scan:

* Pregnancy
* Any health condition that would cause concern that participation would not be in the best interest of health (eg, extensive comorbidities)

Primary outcomes:
measure: Comparison of coronary plaque burden (non-calcified plaque volume (NCPV) measured by CT at 10-years between the initial randomization CT and ICA groups
timeFrame: at 10 years
measure: Comparison of coronary plaque burden total plaque volume (TPV)) measured by CT at 10-years between CT and ICA groups
timeFrame: at 10 years
Secondary outcomes:
measure: Intraindividual progression of coronary artery disease (defined as change in coronary plaque burden from the first CT until the CT examination after 10 years) in the CT group.
timeFrame: at 10 years
measure: Comparison of the difference in chronic kidney injury, (eGFR and as increase in creatinine by 25% or 0.5 mg/dl) in both groups at 10-year follow-up between CT and ICA groups.
timeFrame: at 10 years
Other outcomes:
measure: To compare minor cardiovascular events at final follow-up (after approximately 10 years).
timeFrame: at 10 years
measure: To compare the cost-effectiveness in both groups. (after 10 years).
timeFrame: at 10 years
measure: Comparison of two types of structured reports one medical and one using easy language (according to the german clinical practice guidelines) using patient acceptance questionnaire.
timeFrame: at 10 years
measure: To compare cholesterol level (LDL, HDL, Triglycerin) between the initial randomization CT and ICA groups.
timeFrame: at 10 years
measure: Comparison of statin use (proportion) between the initial randomization CT and ICA groups.
timeFrame: at 10 years
measure: Effect of statins on coronary plaque burden (non-calcified plaque volume (NCPV) )measured by CT at 10-years in CT group
timeFrame: at 10 years
measure: Effect of statins on coronary plaque burden (total plaque volume (TPV)) measured by CT at 10-years in CT group
timeFrame: at 10 years
measure: To compare calcified plaque volume at 10-years between CT and ICA group
timeFrame: at 10 years
measure: To compare low-attenuation plaque volume (LAPV) at 10-years between CT and ICA group
timeFrame: at 10 years
measure: To compare percentage atheroma volume (PAV) at 10-years between CT and ICA group
timeFrame: at 10 years
measure: To compare relative plaque volume at 10-years between CT and ICA group
timeFrame: at 10 years
measure: To compare segment stenosis score (SSS) at 10-years between CT and ICA group
timeFrame: at 10 years
measure: To compare segment involvement score (SIS) at 10-years between CT and ICA group
timeFrame: at 10 years
measure: To compare stenosis at 10-years between CT and ICA group
timeFrame: at 10 years
measure: To compare plaque composition at 10-years between CT and ICA group
timeFrame: at 10 years
measure: To compare high-risk plaque (HRP) features at 10-years between CT and ICA group
timeFrame: at 10 years
measure: To analyze the impact of baseline cardiovascular risk factors on non-calcified plaque volume (NCPV) in the CT Group
timeFrame: at 10 years
measure: To analyze the impact of baseline cardiovascular risk factors on total plaque volume (TPV) in the CT Group
timeFrame: at 10 years
measure: To analyze the impact of nutrition on non-calcified plaque volume (NCPV) in the CT Group
timeFrame: at 10 years
measure: To analyze the impact of nutrition on total plaque volume (TPV) in the CT Group
timeFrame: at 10 years
measure: To analyze the impact of physical activity (Freiburg questionnaire) on non-calcified plaque volume (NCPV) in the CT Group
timeFrame: at 10 years
measure: To analyze the impact of physical activity (Freiburg questionnaire) on total plaque volume (TPV) in the CT Group
timeFrame: at 10 years
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
Study officials:
References:
citation: Dewey M, Rief M, Martus P, Kendziora B, Feger S, Dreger H, Priem S, Knebel F, Bohm M, Schlattmann P, Hamm B, Schonenberger E, Laule M, Zimmermann E. Evaluation of computed tomography in patients with atypical angina or chest pain clinically referred for invasive coronary angiography: randomised controlled trial. BMJ. 2016 Oct 24;355:i5441. doi: 10.1136/bmj.i5441.
citation: Schonenberger E, Martus P, Bosserdt M, Zimmermann E, Tauber R, Laule M, Dewey M. Kidney Injury after Intravenous versus Intra-arterial Contrast Agent in Patients Suspected of Having Coronary Artery Disease: A Randomized Trial. Radiology. 2019 Sep;292(3):664-672. doi: 10.1148/radiol.2019182220. Epub 2019 Jul 2.
citation: Bosserdt M, Martus P, Tauber R, Dreger H, Dewey M, Schonenberger E; CAD-Man Study Group Investigators. Serum creatinine baseline fluctuation and acute kidney injury after intravenous or intra-arterial contrast agent administration-an intraindividual comparison as part of a randomized controlled trial. Nephrol Dial Transplant. 2022 May 25;37(6):1191-1194. doi: 10.1093/ndt/gfac013. No abstract available.
citation: Bosserdt M, Feger S, Rief M, Preuss D, Ibes P, Martus P, Kofoed KF, Laule M, Perez I, Dewey M. Performing Computed Tomography Instead of Invasive Coronary Angiography: Sex Effects in Patients With Suspected CAD. JACC Cardiovasc Imaging. 2020 Mar;13(3):888-889. doi: 10.1016/j.jcmg.2019.10.014. Epub 2019 Dec 18. No abstract available.
citation: Laskowski D, Feger S, Bosserdt M, Zimmermann E, Mohamed M, Kendziora B, Rief M, Dreger H, Estrella M, Dewey M. Detection of relevant extracardiac findings on coronary computed tomography angiography vs. invasive coronary angiography. Eur Radiol. 2022 Jan;32(1):122-131. doi: 10.1007/s00330-021-07967-x. Epub 2021 Jun 15.
citation: Feger S, Elzenbeck L, Rieckmann N, Marek A, Dreger H, Beling M, Zimmermann E, Rief M, Chow BJW, Maurovich-Horvath P, Laule M, Tauber R, Dewey M. Effect of Computed Tomography Versus Invasive Coronary Angiography on Statin Adherence: A Randomized Controlled Trial. JACC Cardiovasc Imaging. 2021 Jul;14(7):1480-1483. doi: 10.1016/j.jcmg.2021.01.032. Epub 2021 May 19. No abstract available.