Magnetic Nanoparticles System in Acute Coronary Syndrome

The Development and Clinical Application of Rapid Assays Using Multi-antibody-activated Magnetic Nanoparticles System in Acute Coronary Syndrome

To improve the sensitivity and specificity of immunoassay, the developing trends are to lower the detection threshold and to minimize the cross reaction. A new assay technology called immunomagnetic reduction (IMR) has been developed for rapid and on-site assay with small volume of sample. Rapid diagnosis of acute coronary syndrome (ACS) is a clinical and operational priority in busy emergency departments (ED), early and correct diagnosis is important. Cardiac enzymes (including CPK/CK-MB, troponins, myoglobulin) and electrocardiography (ECG) in combination with the medical history and physical examination are at present the diagnostic cornerstones. Novel biomarkers that rise earlier, have good diagnosis accuracy and have additional prognostic information are highly needed. The combination of multiple biomarker assays (markers of myocardial injury, inflammation/plaque ruptures or heart failure with different mechanism) may increase clinical sensitivity and improve early risk stratification. The present study, a rapid IMR assay with multiple biomarkers is proposed and we will examine the performance of this new investigational IMR assays, comparison with current commercial assays.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome

Detailed Description

To improve the sensitivity and specificity of immunoassay, the developing trends are to lower the detection threshold and to minimize the cross reaction. A new assay technology called immunomagnetic reduction (IMR) has been developed for rapid and on-site assay with very small volume of sample (i.e. less than 1ml whole blood). The reagent is a solution of homogeneously dispersed magnetic nanoparticles, which are coated with hydrophilic surfactants and bioprobes. Under external multiple alternating-current (ac) magnetic fields, magnetic nanoparticles oscillate with the multiple ac magnetic fields via magnetic interaction. The reagents under the external multiple ac magnetic fields show a magnetic property, called mixed-frequency ac magnetic susceptibility χac. Magnetic nanoparticles bind with the bioprobes on the outmost shell and become larger or clustered. The χac of the reagent is reduced, and the concentration of the biomolecules can be measured quantitatively. Several papers have demonstrated that IMR can be applied to assay proteins, viruses, chemicals, and nucleic acids once suitable bioprobes are immobilized onto the magnetic nanoparticles.

Rapid diagnosis of acute coronary syndrome (ACS) is a clinical and operational priority in busy emergency departments (ED). Since ACS is associated with a significant mortality and morbidity, early and correct diagnosis is of great importance. Chest pain is a frequent symptom in medical emergency departments and distinguishing patients with ACS within the chest pain group is a diagnostic challenge. Cardiac enzymes (including CPK/CK-MB, troponins, myoglobulin) and electrocardiography (ECG) in combination with the medical history and physical examination are at present the diagnostic cornerstones. Different cardiac enzymes are released after myocardial cell disintegration and are markers of cell necrosis, which might not be detected immediately after chest pain; and repeated measurements are suggested. Therefore novel biomarkers that rise earlier, have good diagnosis accuracy and have additional prognostic information are highly needed. Some publications address the potential benefit of the combination of multiple biomarker assays (markers of myocardial injury, inflammation/plaque ruptures or heart failure with different mechanism) could substantially increase clinical sensitivity and improve early risk stratification. However, this approach is rather time-consuming and not cost-effect. In the present study, a rapid IMR assay with multiple biomarkers is proposed and we will examine the performance of this new investigational IMR assays, comparison with current commercial assays.

• Study Type: Observational
• Enrollment (Actual): 455

Contacts and Locations

Study Locations

• Taiwan
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 33004
    • Taoyuan General Hospital, Ministry of Health and Welfare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with acute chest pain who are sent to the emergency departments will be included

Description

Inclusion Criteria:

• Diagnosis with acute coronary syndrome

Exclusion Criteria: none

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnositic accuracy of acute myocardial infarction	Evaluation of the diagnostic performance of rapid IMR assays in detection of acute myocardial infarction; Cardiac enzymes (CPK/CK-MB, troponins), electrocardiography in combination with the symptoms of typical chest pain are at present the diagnostic gold standard.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combination of potential biomarkers in detection of ACS by rapid IMR system	Compared to cardiac enzymes (CK/CK-MB, troponin), the diagnostic performance of combination of new biomarkers (BNP, FABP4, CRP, etc.) in detection of ACS by rapid IMR system	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of MACEs by rapid IMR system	Evaluation of prognostic significance of multi-antibody-activated magnetic nanoparticles system (troponin, CK-MB, myoglobin, BNP, CRP, adipocyte fatty-acid binding protein/FABP-4) in acute coronary syndrome	6 months

Collaborators and Investigators

• Sponsor: Far Eastern Memorial Hospital
• Collaborators: National Taiwan University Hospital
• Investigators: Principal Investigator: Yen-Wen Wu, MD, PhD, Far Eastern Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: August 25, 2014
• First Submitted That Met QC Criteria: August 26, 2014
• First Posted (Estimated): August 27, 2014

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 24, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: acute coronary syndrome; serum biomarkers; immunomagnetic reduction
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome
• Other Study ID Numbers: 103002_N_103CT1026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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