The "CAD-Man" EXTEND Study (CAD-Man-EXTEND)

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Diagnostic test: CT; Diagnostic test: invasive coronary angiography (ICA)

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.

• Study Type: Interventional
• Enrollment (Actual): 318
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CT; CT-directed clinical management strategy	Diagnostic test: CT; CT-directed clinical management strategy
Active Comparator: Invasive coronary angiography (ICA); Standard clinical management directed by conventional invasive coronary angiography (ICA).	Diagnostic test: invasive coronary angiography (ICA); Standard clinical management directed by conventional invasive coronary angiography (ICA).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Comparison of coronary plaque burden total plaque volume (TPV)) measured by CT at 10-years between CT and ICA groups	at 10 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
To compare cholesterol level (LDL, HDL, Triglycerin) between the initial randomization CT and ICA groups.		at 10 years
Comparison of statin use (proportion) between the initial randomization CT and ICA groups.		at 10 years
Effect of statins on coronary plaque burden (non-calcified plaque volume (NCPV) )measured by CT at 10-years in CT group		at 10 years
Effect of statins on coronary plaque burden (total plaque volume (TPV)) measured by CT at 10-years in CT group		at 10 years
To compare calcified plaque volume at 10-years between CT and ICA group		at 10 years
To compare low-attenuation plaque volume (LAPV) at 10-years between CT and ICA group		at 10 years
To compare percentage atheroma volume (PAV) at 10-years between CT and ICA group		at 10 years
To compare relative plaque volume at 10-years between CT and ICA group		at 10 years
To compare segment stenosis score (SSS) at 10-years between CT and ICA group		at 10 years
To compare segment involvement score (SIS) at 10-years between CT and ICA group		at 10 years
To compare stenosis at 10-years between CT and ICA group	Stenosis (no stenosis, <20%, 20 to 50%, >50%)	at 10 years
To compare plaque composition at 10-years between CT and ICA group	(calcified, non-calcified (fibrous, fibrofatty, lipid-rich), partially calcified)	at 10 years
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
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
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
To analyze the impact of nutrition on non-calcified plaque volume (NCPV) in the CT Group		at 10 years
To analyze the impact of nutrition on total plaque volume (TPV) in the CT Group		at 10 years
To analyze the impact of physical activity (Freiburg questionnaire) on non-calcified plaque volume (NCPV) in the CT Group		at 10 years
To analyze the impact of physical activity (Freiburg questionnaire) on total plaque volume (TPV) in the CT Group		at 10 years

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Actual): January 11, 2025
• Study Completion (Actual): January 29, 2026

Study Registration Dates

• First Submitted: December 20, 2023
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): February 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease
• Other Study ID Numbers: EA1/124/23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share individual patient data from CAD-Man extend study via the GUIDE-IT platform.
• IPD Sharing Time Frame: 12 months after publication. End 3 years after publication

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal approved by the Dissemination Committee of CAD-Man and GUIDE-IT.

The study proposal must include: The proposed study's overview, rationale, aims and analysis methods, plans for dissemination of results and names of those wishing to access data, and how is the data going to be stored and for how long.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No