Personalized Evaluation of Susptected Myocardial Ischemia

NCT ID: NCT06708000

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Clinical Phase

PHASE3

Total Enrollment

2000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-20

Study Completion Date

2027-12-31

Brief Summary

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This study aims to assess whether the use of clinical risk models, known as Clinical Likelihood (CL) models, can reduce the need for diagnostic examinations without negatively impacting quality of life or prognosis after 12 months in patients with stable new onset chest pain. Additionally, the project will evaluate a newly developed method called Laser Speckle Contrast Imaging for measuring function and oxygen content in the smallest blood vessels (microvasculature) of the hand, which may also reflect blood flow and oxygen content in the microvasculature of the heart.

Detailed Description

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Ischemic heart disease poses a significant burden on society and affects many Danes annually. With more than 300,000 citizens in Denmark living with cardiovascular disease, and more than 17,500 cardiovascular deaths annually, the need for effective diagnosis and treatment is crucial. Cardiac Computed Tomography Angiography (CCTA) has become an important tool in diagnosing arteriosclerotic obstructive coronary artery disease (CAD) in patients with typical or atypical chest pain, but the increasing use of this method requires a more efficient selection of patients before initial testing. Early and accurate risk stratification could improve patient management, reduce morbidity, and improve patient outcomes, highlighting the importance of optimizing diagnostic pathways.

At Gødstrup Hospital, novel clinical likelihood (CL) models have been developed to assess the pre-test probability of obstructive CAD. Based on sex, age, and symptom characteristics, and including traditional cardiovascular risk factors, the risk factor-weighted clinical likelihood (RF-CL) model improves discrimination of obstructive CAD and prognosis compared to traditional models. Additionally, the utilization of a coronary artery calcium score (CACS) in conjunction with the RF-CL model, i.e., the CACS-weighted clinical likelihood (CACS-CL) model, further enhances patient management in external validation cohorts. Recently, both CL models have been implemented in the European guidelines on CAD management. However, the CL models have only been applied in observational studies, and no randomized trials substantiate their use in clinical practice.

It is hypothesized that a diagnostic strategy based on an assessment including the CL models is non-inferior to the current standard strategy, as measured by the number of asymptomatic patients during follow-up. Secondly, it is assumed that the CL-based strategy reduces unnecessary diagnostic tests and improve resource utilization without compromising patient safety.

Emerging alongside these developments is Laser Speckle Contrast Imaging (LSCI), a promising non-invasive technique for assessing microvascular function. Several studies have suggested a link between reduced microcirculation in the skin and heart among patients with angina and non-significant calcification, compared to healthy controls. LSCI measures red blood cell movement to quantify blood flow, making it an effective, fast, and cost-efficient tool already in use in other medical fields. If a correlation between peripheral and cardiac microcirculation is established, LSCI could address a diagnostic gap in detecting microvascular dysfunction, particularly for angina patients without significant coronary calcification. Integrating LSCI into the diagnostic process offers potential to further refine patient selection for testing and provide more targeted diagnostic pathways.

This study will increase the evidence for utilizing the RF-CL and CACS-CL models in clinical practice. Currently, the use of pre-test likelihood models is only recommended with a IB recommendation and deferral of diagnostic testing in individuals with CL\>=5% with IIa B recommendation due to a lack of randomized studies. The study will focus on symptomatic endpoints and investigate quality of life measurements in patients deferred for testing based on the CL estimation. Secondary endpoints include both effectiveness and safety metrics.

This project is an ambitious endeavor that builds on previous work performed within our research group. The supervisors are experienced researchers with substantial expertise in this area and conducting randomized studies. The findings from this study have the potential to significantly impact clinical practice by providing evidence-based recommendations (Level/Class of evidence 1A) for the use of CL models in the diagnostic pathway of ischemic heart disease.

By demonstrating that using the CL model in the management of patients with new-onset chest pain substantially and safely reduces the necessity for cardiac CT and other advanced diagnostic procedures, resource utilization could improve and costs be lowered for the healthcare system. Additionally, as tests could be deferred without compromising safety, patient-related quality of life could improve. Finally, the findings are expected to contribute to clinical guidelines and practices, benefiting the broader field of cardiology. By validating the CL models in a large, diverse patient population, this study could provide strong evidence for their broader implementation in clinical practice.

The incorporation of LSCI into this framework also presents an exciting avenue for further improving diagnostic precision. If LSCI can reliably identify microvascular dysfunction, it could serve as a complementary tool in optimizing diagnostic strategies, particularly for patients in whom obstructive CAD has been ruled out but who still experience angina-like symptoms.

If CL model utilization proves capable of safely reducing the necessity for CCTA and other advanced diagnostic procedures in patients with obstructive CAD, resource utilization could improve, lowering costs for the healthcare system while maintaining or enhancing patient quality of life.

The present research addresses a significant gap in current diagnostic strategies and has the potential to shift clinical practices towards more personalized and efficient care pathways for stable chest pain.

Conditions

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Chronic Coronary Syndrome Angina Pectoris Coronary Artery Disease Myocardial Ischemia Arteriosclerosis

Keywords

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Chronic Coronary Syndrome Angina Pectoris Coronary Artery Disease Clinical Likelihood Myocardial Ischemia PERMI

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The project is a randomized, multi-centre interventional study that includes patients without prior evaluation for obstructive CAD who are referred for cardiac CT based on clinically suspected stable ischemic heart disease. Participants are 1:1 randomized into either an intervention group where patient management relies on an initial CL evaluation, or a control group that adheres to current standard diagnostic procedures. This design allows for direct comparison of outcomes between the new and existing diagnostic strategies.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

SINGLE

Investigators
The randomization will be conducted in a 1:1 ratio using an internet-based randomization solution.

Then, patients will be randomly assigned to either the control group or the intervention group, and regardless of study allocation and initial RF-CL assessement, all patients will then receive an initially blinded CCTA. The cardiologist conducting the CCTA is unaware of the patient's randomization status.

Patients in the intervention group with a clinical likelihood of obstructive CAD (RF-CL) ≤5% will receive a blinded CCTA.

Patients in the intervention group with RF-CL \>5% will undergo a CACS assessment to estimate a CACS-CL.

Patients in the control group, and patients in the intervention group with a CL \>5%, will receive their test results, including unblinding of the results from the CCTA.

Patients in the intervention group with CL≤5% will also receive their test results, except for the CCTA results which remain blinded.

The interviewer at follow-up is unaware of the CCTA result.

Study Groups

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Clinical Likelihood-Based Diagnostic Strategy

Patients in this arm will be assessed using the Clinical Likelihood (CL) models, including the Risk Factor-Weighted Clinical Likelihood (RF-CL) and Coronary Artery Calcium Score-Weighted Clinical Likelihood (CACS-CL) models.

Group Type EXPERIMENTAL

Clinical Likelihood (CL) Model-Based Diagnostic Strategy

Intervention Type DIAGNOSTIC_TEST

The Clinical Likelihood (CL) model-based diagnostic strategy utilizes two models: the RF-CL model and the CACS-CL model. These models assess the pre-test probability of obstructive coronary artery disease (CAD) based on patient factors such as age, sex, symptoms, and traditional cardiovascular risk factors like smoking, diabetes, and hypertension. The CACS-CL model incorporates coronary artery calcium scoring to further refine the risk assessment. Patients identified with a low likelihood of CAD may avoid unnecessary diagnostic testing, such as cardiac CT, while maintaining diagnostic accuracy and safety. This approach aims to optimize resource use, reduce patient burden, and focus on other potential causes of symptoms when CAD is unlikely.

Standard of Care

Patients in this arm will follow the standard diagnostic pathway.

Group Type ACTIVE_COMPARATOR

Standard of care treatment

Intervention Type DIAGNOSTIC_TEST

Patients will follow the standard diagnostic pathway, which includes the use of cardiac CT and other advanced diagnostic procedures based on clinical guidelines. This approach is the current standard of care for patients with suspected obstructive coronary artery disease (CAD). The control group allows for comparison of outcomes with those in the intervention arm, particularly in terms of resource utilization, patient safety, and diagnostic accuracy.

Interventions

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Clinical Likelihood (CL) Model-Based Diagnostic Strategy

The Clinical Likelihood (CL) model-based diagnostic strategy utilizes two models: the RF-CL model and the CACS-CL model. These models assess the pre-test probability of obstructive coronary artery disease (CAD) based on patient factors such as age, sex, symptoms, and traditional cardiovascular risk factors like smoking, diabetes, and hypertension. The CACS-CL model incorporates coronary artery calcium scoring to further refine the risk assessment. Patients identified with a low likelihood of CAD may avoid unnecessary diagnostic testing, such as cardiac CT, while maintaining diagnostic accuracy and safety. This approach aims to optimize resource use, reduce patient burden, and focus on other potential causes of symptoms when CAD is unlikely.

Intervention Type DIAGNOSTIC_TEST

Standard of care treatment

Patients will follow the standard diagnostic pathway, which includes the use of cardiac CT and other advanced diagnostic procedures based on clinical guidelines. This approach is the current standard of care for patients with suspected obstructive coronary artery disease (CAD). The control group allows for comparison of outcomes with those in the intervention arm, particularly in terms of resource utilization, patient safety, and diagnostic accuracy.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Patients with de novo chest pain referred on suspicion of stable ischemic CAD
* Patients capable of providing written informed consent

Exclusion Criteria

* Age \<30 years or \>75 years
* Known ischemic heart disease, including previous PCI (with or without stent) and bypass surgery
* Unstable angina pectoris at initial consultation
* Severe COPD or asthma
* Severe valvular disease
* Absolute or relative contraindications for Cardiac CT:
* allergy to iomeron
* pregnant women, including women who are potentially pregnant or lactating
* reduced kidney function with an estimated glomerular filtration rate \<40 ml/min
* LVEF \<45%
Minimum Eligible Age

30 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gødstrup Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Regional Hospital of Godstrup

Herning, , Denmark

Site Status

Countries

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Denmark

References

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Winther S, Schmidt SE, Mayrhofer T, Botker HE, Hoffmann U, Douglas PS, Wijns W, Bax J, Nissen L, Lynggaard V, Christiansen JJ, Saraste A, Bottcher M, Knuuti J. Incorporating Coronary Calcification Into Pre-Test Assessment of the Likelihood of Coronary Artery Disease. J Am Coll Cardiol. 2020 Nov 24;76(21):2421-2432. doi: 10.1016/j.jacc.2020.09.585.

Reference Type BACKGROUND
PMID: 33213720 (View on PubMed)

Brix GS, Rasmussen LD, Rohde PD, Schmidt SE, Nyegaard M, Douglas PS, Newby DE, Williams MC, Foldyna B, Knuuti J, Bottcher M, Winther S. Calcium Scoring Improves Clinical Management in Patients With Low Clinical Likelihood of Coronary Artery Disease. JACC Cardiovasc Imaging. 2024 Jun;17(6):625-639. doi: 10.1016/j.jcmg.2023.11.008. Epub 2024 Jan 3.

Reference Type BACKGROUND
PMID: 38180413 (View on PubMed)

Rasmussen LD, Fordyce CB, Nissen L, Hill CL Jr, Alhanti B, Hoffmann U, Udelson J, Bottcher M, Douglas PS, Winther S. The PROMISE Minimal Risk Score Improves Risk Classification of Symptomatic Patients With Suspected CAD. JACC Cardiovasc Imaging. 2022 Aug;15(8):1442-1454. doi: 10.1016/j.jcmg.2022.03.009. Epub 2022 May 11.

Reference Type BACKGROUND
PMID: 35926903 (View on PubMed)

Rasmussen LD, Williams MC, Newby DE, Dahl JN, Schmidt SE, Bottcher M, Winther S. External validation of novel clinical likelihood models to predict obstructive coronary artery disease and prognosis. Open Heart. 2023 Dec 6;10(2):e002457. doi: 10.1136/openhrt-2023-002457.

Reference Type BACKGROUND
PMID: 38056915 (View on PubMed)

Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. No abstract available.

Reference Type BACKGROUND
PMID: 39210710 (View on PubMed)

Other Identifiers

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1-10-72-47-24

Identifier Type: -

Identifier Source: org_study_id