Optimal Evaluation to Reduce Imaging Testing (OPERATE)

Optimal Evaluation of Stable Chest Pain to Reduce Unnecessary Utilization of Cardiac Imaging Testing

In daily clinical routine, the evaluation of new-onset and stable chest pain (SCP) suggestive of chronic coronary syndrome (CCS) remains a challenge for physicians. Although coronary computed tomography angiography (CCTA) seems to be the first-line cardiac imaging testing (CIT) according to the recommendations from current guidelines, the optimal diagnostic strategy to identify low risk patients who may derive minimal benefit from further CIT is the cornerstone of clinical management for SCP. Recently, different diagnostic strategies were provided to effectively defer unnecessary CIT, but few studies have prospectively determined the actual effect of applying these strategies in clinical practice. Therefore, the OPERATE study was designed to compare the effectiveness and safety of two proposed diagnostic strategies in identification of low risk individual who may derive minimal benefit from CCTA among patients with SCP suggestive of CCS in a pragmatic randomized controlled trial (RCT).

Study Overview

• Status: Recruiting
• Conditions: Chronic Coronary Syndrome
• Intervention / Treatment: Diagnostic test: 2019 ESC guideline-determined diagnostic strategy; Diagnostic test: 2016 NICE guideline-determined diagnostic strategy

Detailed Description

OPERATE trial was an investigator-initiated, multicenter, prospective, CCTA-based, 2-arm 1:1 parallel-group, double-blind and pragmatic RCT planned to include 800 subjects with SCP suggestive of CCS. Subjects were assigned randomly to two groups: 1) 2016 National Institutes for Clinical Excellence guidelines-determined diagnostic strategy (NICE strategy) and 2) 2019 European Society of Cardiology guidelines-determined diagnostic strategy (ESC strategy) The primary objective of OPERATE trial is to compare the rates of CCTA without obstructive CAD according to NICE and ESC strategy. The key secondary objective is to assess whether the two strategies have no significant difference in terms of major adverse cardiac events (MACE). The investigators hypothesize that when comparing with NICE strategy, ESC strategy which sequentially incorporated the ESC-PTP model with RF-CL model will decrease the probability of CCTA without obstructive CAD but not at the expense of safety and cost over a follow-up period of 1 year.

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jia Zhou, MD; Phone Number: +8615522485560; Email: zhoujiawenzhang@126.com

Study Locations

• China
  • Tianjin, China, 300000
    • Recruiting
    • Tianjin Chest Hospital
    • Contact: Jia Zhou; Phone Number: +15522485560; Email: zhoujiawenzhang@126.com
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Chaoyang Hospital
      • Contact: Yahang Tan
  • Hebei
    • Lanfang, Hebei, China
      • Recruiting
      • Hebei Petrochina Central Hospital
      • Contact: Tao Cheng
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin First Central Hospital
      • Contact: Ting Xin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. SCP or equivalenta suggestive of CCS and clinically stability
2. No history of CAD (prior myocardial infarction, CR or any CAD documented by previous CIT)
3. Age ≥30 years
4. Willing and able to provide informed consent

Exclusion criteria

1. Prior CIT within 1 year prior to randomization
2. Clinically instability (e.g. cardiogenic shock, ACS, severe arrhythmias or NYHA III or IV heart failure)
3. Non-sinus rhythm
4. Concomitant participation in another clinical trial
5. Complex structural heart disease
6. Non-cardiac illness with life expectancy < 2 years
7. Allergy to iodinated contrast agent
8. Estimated glomerular filtration rate<60 ml/min/1.73m2 within 90 days
9. Body mass index >35kg/m2
10. Expressing a clear preference for undergoing CIT or not
11. Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ESC strategy; ESC-PTP is calculated using age, sex and type of chest pain according to 2019 ESC guideline for the diagnosis and management of CCS and RF-CL is calculated using age, sex, type of chest pain, hypertension, dyslipidemia, diabetes, smoking and family history of CAD based on the publication of Winther et al., respectively. According to ESC strategy, subjects with ESC-PTP ≤5% are classified into low risk group and ones with ESC-PTP ≥15% are classified into high risk group. For subjects with ESC-PTP of 5%-15%, ones with RF-CL ≥15% are classified into high risk group and ones with RF-CL <15% are classified into low risk group. CCTA should be referred for a subject in high risk group. Subjects determined to be at low risk will be referred to optimal medication treatment with no immediate CCTA.	Diagnostic test: 2019 ESC guideline-determined diagnostic strategy; ESC-PTP is calculated using age, sex and type of chest pain according to 2019 ESC guideline for the diagnosis and management of CCS and RF-CL is calculated using age, sex, type of chest pain, hypertension, dyslipidemia, diabetes, smoking and family history of CAD based on the publication of Winther et al., respectively. According to ESC strategy, subjects with ESC-PTP ≤5% are classified into low risk group and ones with ESC-PTP ≥15% are classified into high risk group. For subjects with ESC-PTP of 5%-15%, ones with RF-CL ≥15% are classified into high risk group and ones with RF-CL <15% are classified into low risk group. CCTA should be referred for a subject in high risk group. Subjects determined to be at low risk will be referred to optimal medication treatment with no immediate CCTA.
Experimental: NICE strategy; According to NICE strategy, subjects with nonanginal chest pain and normal ECG are classified into low risk group and ones with typical and atypical angina or nonanginal chest pain with abnormal ECG are classified into high risk group. CCTA should be referred for a subject in high risk group. Subjects determined to be at low risk will be referred to optimal medication treatment with no immediate CCTA.	Diagnostic test: 2016 NICE guideline-determined diagnostic strategy; For subjects assigned to NICE strategy, ones with nonanginal chest pain and normal ECG were classified into low risk group and ones with typical and atypical angina or nonanginal chest pain with abnormal ECG were classified into high risk group. Subjects determined to be at low risk will be referred to optimal medication treatment with no immediate CCTA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CCTA without obstructive CAD	The summary of nonobstructive CAD, no sign of CAD and nondiagnostic result detected by CCTA according to each strategy	Through the initial management, an average of 2-5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACE	All-cause death, myocardial infarction and hospitalization due to unstable angina.	1 year
All-cause death	Any death.	1 year
Myocardial infarction	Myocardial infarction was defined and classified as spontaneous or coronary procedure-related MI according to the Fourth Universal Definition of Myocardial Infarction.	1 year
Hospitalization due to unstable angina	An hospitalization event in which the final diagnosis was myocardial ischemia.	1 year
Exposure to radiation	All exposure to radiation related to CIT and other cardiovascular procedures.	1 year
Procedural complications	All procedural complications related to CIT and other cardiovascular procedures.	1 year
Cumulative proportion of patients receiving other CITs		1 year
Cumulative proportion of patients receiving CR		1 year
Cumulative proportion of patients who had alteration in OMT based on results of CCTA		Thtough the initial management, an average of 2-5 days
Proportion of normal CCTA		Through the initial management, an average of 2-5 days
Proportion of necessary CCTA		Through the initial management, an average of 2-5 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The health-related quality of life assessment (SAQ)	Seattle Angina Questionnaire	1 year
The health-related quality of life assessment (EQ-5D)	Visual-analogue scale of the European Quality of Life-5 Dimensions	1 year

Collaborators and Investigators

• Sponsor: Tianjin Chest Hospital
• Investigators: Principal Investigator: Jia Zhou, MD, Tianjin Chest Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2023
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: November 27, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 23, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Stable Chest Pain; Pretest Probability; Coronary Computed Tomography Angiography; Diagnostic Strategy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chest Pain
• Other Study ID Numbers: 2022KY-024-01; 62206197 (Other Grant/Funding Number: National Natural Science Foundation of China); TJWJ2022QN067 (Other Grant/Funding Number: Tianjin Health Research Project); 21JCYBJC00820 (Other Grant/Funding Number: Applied and Basic Research by Multi-input Foundation of Tianjin)

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