The "CAD-Man" EXTEND Study

Coronary Artery Disease Clinical Trial

— CAD-Man-EXTEND  

Official title:

A Randomized, Controlled Trial in Patients With Suspected Coronary Artery Disease Based on Acute or Chronic Atypical Angina Pectoris - EXTEND

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06237673
• Other study ID #: EA1/124/23
• Status: Enrolling by invitation
• Phase: N/A
• Start date: December 1, 2023
• Est. completion date: January 15, 2026

Study information

• Verified date: January 2024
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 318
• Est. completion date: January 15, 2026
• Est. primary completion date: January 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Diagnostic Test:
• CT
CT-directed clinical management strategy
• invasive coronary angiography (ICA)
Standard clinical management directed by conventional invasive coronary angiography (ICA).

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (6)

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. — View 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. — View 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. Erratum In: BMJ. 2016 Nov 29;355:i6420. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To compare minor cardiovascular events at final follow-up (after approximately 10 years).	Cardiovascular events (unstable angina pectoris, re-revascularization, and first revascularization at least 2 months after randomization)	at 10 years
Other	To compare the cost-effectiveness in both groups. (after 10 years).	To compare cost-effectiveness in both groups using the quality-adjusted life year data, and cost data derived from the trial.	at 10 years
Other	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.		at 10 years
Other	To compare cholesterol level (LDL, HDL, Triglycerin) between the initial randomization CT and ICA groups.		at 10 years
Other	Comparison of statin use (proportion) between the initial randomization CT and ICA groups.		at 10 years
Other	Effect of statins on coronary plaque burden (non-calcified plaque volume (NCPV) )measured by CT at 10-years in CT group		at 10 years
Other	Effect of statins on coronary plaque burden (total plaque volume (TPV)) measured by CT at 10-years in CT group		at 10 years
Other	To compare calcified plaque volume at 10-years between CT and ICA group		at 10 years
Other	To compare low-attenuation plaque volume (LAPV) at 10-years between CT and ICA group		at 10 years
Other	To compare percentage atheroma volume (PAV) at 10-years between CT and ICA group		at 10 years
Other	To compare relative plaque volume at 10-years between CT and ICA group		at 10 years
Other	To compare segment stenosis score (SSS) at 10-years between CT and ICA group		at 10 years
Other	To compare segment involvement score (SIS) at 10-years between CT and ICA group		at 10 years
Other	To compare stenosis at 10-years between CT and ICA group	Stenosis (no stenosis, <20%, 20 to 50%, >50%)	at 10 years
Other	To compare plaque composition at 10-years between CT and ICA group	(calcified, non-calcified (fibrous, fibrofatty, lipid-rich), partially calcified)	at 10 years
Other	To compare high-risk plaque (HRP) features at 10-years between CT and ICA group	(HRP; positive remodelling (PR), napkin ring sign, spotty calcification, low attenuation (LAP)	at 10 years
Other	To analyze the impact of baseline cardiovascular risk factors on non-calcified plaque volume (NCPV) in the CT Group	Age (< 65, 65-75, > 75); Body Mass Index (BMI) (< 25, 25-30, > 30) Gender (male versus female) Diabetes (yes/no)	at 10 years
Other	To analyze the impact of baseline cardiovascular risk factors on total plaque volume (TPV) in the CT Group	Age (< 65, 65-75, > 75); Body Mass Index (BMI) (< 25, 25-30, > 30) Gender (male versus female) Diabetes (yes/no)	at 10 years
Other	To analyze the impact of nutrition on non-calcified plaque volume (NCPV) in the CT Group		at 10 years
Other	To analyze the impact of nutrition on total plaque volume (TPV) in the CT Group		at 10 years
Other	To analyze the impact of physical activity (Freiburg questionnaire) on non-calcified plaque volume (NCPV) in the CT Group		at 10 years
Other	To analyze the impact of physical activity (Freiburg questionnaire) on total plaque volume (TPV) in the CT Group		at 10 years
Primary	Comparison of coronary plaque burden (non-calcified plaque volume (NCPV) measured by CT at 10-years between the initial randomization CT and ICA groups		at 10 years
Primary	Comparison of coronary plaque burden total plaque volume (TPV)) measured by CT at 10-years between CT and ICA groups		at 10 years
Secondary	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.		at 10 years
Secondary	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.		at 10 years