Rule Out of ACS in Primary Care Using a Decision Rule for Chest Pain Including Hs-troponin I POCT (POB HELP)

Primary Care Decision Rule for Chest Pain Using the Marburg Heart Score and Hs-troponin I Point of Care Test to Rule Out Acute Coronary Syndrome

The goal of this clustered, diagnostic randomized controlled trial is to study a clinical decision rule including a high-sensitive troponin I point of care test in patients with chest pain in primary care.

The main questions it aims to answer are:

1. Can unnecessary referrals to secondary care be reduced by the use of a clinical deci-sion rule in patients with new onset, non-traumatic chest pain in primary care? Compared to current daily practice.
2. What is the accuracy (sensitivity, negative prediction value) of the clinical decision rule for excluding ACS and MACE at 6 weeks and 6 months?

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Chest Pain; Acute Coronary Syndrome
• Intervention / Treatment: Diagnostic test: Clinical decision rule

Detailed Description

This clustered, diagnostic randomized controlled trial will included patients with acute chest pain consulting their general practitioner. Practices in the intervention group will use a clinical decision rule consisting of the Marburg Heart Score and a high-sensitive troponin I point of care test to exclude acute coronary syndrome (ACS) and decide upon referral. Practices in the control group will apply usual care following local guidelines.

An independent endpoint committee consisting of a cardiologist and general practitioner will adjudicate the final diagnosis. Primary endpoints are ACS and Major Adverse Cardiac Events. A delayed reference standard of 6 months will be used.

For high sensitive troponin I measurement, the Siemens Atellica VTLi immunoassay analyser is used.

• Study Type: Interventional
• Enrollment (Actual): 946
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • South Holland
    • Leiden, South Holland, Netherlands, 2300 RC
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ≥18 years of age
• Acute chest pain
• Seen by general practitioner

Exclusion Criteria:

• <1 hour since onset of symptoms
• Inability to speak or understand Dutch
• Hemodynamic instability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clinical decision rule; Patients in whom the clinical decision rule is used to exclude acute coronary syndrome	Diagnostic test: Clinical decision rule; Clinical decision rule for acute chest pain, consisting of the Marburg Heart Score (5 questions) combined with a high-sensitive troponin I point of care test
No Intervention: Standard care; Patients in whom the general practitioner decides upon referral following local guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital referral rate for acute chest pain	hospital referral rate for acute chest pain compared between intervention and control group	24 hours after inclusion
Hospital referral rate for acute chest pain	hospital referral rate for acute chest pain compared between intervention and control group	6 weeks after inclusion
Diagnostic accuracy of the clinical decision rule	Diagnostic accuracy (i.e. sensitivity, negative predictive value) for Acute Coronary Syndrome (ACS) and major adverse cardiac events (MACE). MACE is defined as a combined endpoint of ACS, percutaneous coronary intervention, coronary artery bypass grafting, coronary angiography revealing procedurally correctable stenosis managed conservatively and all-cause mortality.	24 hours after inclusion
Diagnostic accuracy of the clinical decision rule	Diagnostic accuracy (i.e. sensitivity, negative predictive value) for ACS and major adverse cardiac events (MACE) MACE is defined as a combined endpoint of ACS, percutaneous coronary intervention, coronary artery bypass grafting, coronary angiography revealing procedurally correctable stenosis managed conservatively and all-cause mortality.	6 weeks after inclusion
Diagnostic accuracy of the clinical decision rule	Diagnostic accuracy (i.e. sensitivity, negative predictive value) for ACS and major adverse cardiac events (MACE) MACE is defined as a combined endpoint of ACS, percutaneous coronary intervention, coronary artery bypass grafting, coronary angiography revealing procedurally correctable stenosis managed conservatively and all-cause mortality.	6 months after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-effectiveness	A trial-based cost analysis and a cost-utility analysis (costs per QALY, assessed using the EQ-5D-5L questionnaire)	6 months
Patient reassurance measured by the State-Trait Anxiety Inventory	Reassurance of patients, using the State-Trait Anxiety Inventory after the index consultation. State-Trait Anxiety Inventory: consisting of 40 self-report items on a 4-point Likert scale (min. 20- max. 80 points). Higher scores are correlated with higher levels of anxiety. Compared between intervention and control group.	1 week after inclusion
Diagnostic accuracy of the HEART-score	Retrospectively for all patient with an ECG available for the occurrence of Acute Coronary Syndrome (ACS) and MACE. HEART-score assigning 0, 1 or 2 points to patient history, ECG abnormalities, Age, Cardiovascular risk factors and troponin. Lower score (0-3) indicates low risk for acute cardiac event. MACE is defined as a combined endpoint of ACS, percutaneous coronary intervention, coronary artery bypass grafting, coronary angiography revealing procedurally correctable stenosis managed conservatively and all-cause mortality.	6 weeks after inclusion
Subgroup analyses for hospital referral rate for acute chest pain	Subgroups are classified by; sex; region (Leiden, Maastricht, Venlo); socio-economic status (using postal-code); duration of symptoms (<2 hours, 2-6 hours, 6-12 hours, >12 hours, >24 hours)	24 hours after inclusion
Subgroup analyses for hospital referral rate for acute chest pain	Subgroups are classified by; sex; region (Leiden, Maastricht, Venlo); socio-economic status (using postal-code); duration of symptoms (<2 hours, 2-6 hours, 6-12 hours, >12 hours, >24 hours)	6 weeks after inclusion
Subgroup analyses for diagnostic accuracy of the clinical decision rule	Subgroups are classified by; sex; region (Leiden, Maastricht, Venlo); socio-economic status (using postal-code); duration of symptoms (<2 hours, 2-6 hours, 6-12 hours, >12 hours, >24 hours) For the occurrence of ACS and MACE. MACE is defined as a combined endpoint of ACS, percutaneous coronary intervention, coronary artery bypass grafting, coronary angiography revealing procedurally correctable stenosis managed conservatively and all-cause mortality.	24 hours after inclusion
Subgroup analyses for diagnostic accuracy of the clinical decision rule	Subgroups are classified by; sex; region (Leiden, Maastricht, Venlo); socio-economic status (using postal-code); duration of symptoms (<2 hours, 2-6 hours, 6-12 hours, >12 hours, >24 hours) For the occurrence of ACS and MACE. MACE is defined as a combined endpoint of ACS, percutaneous coronary intervention, coronary artery bypass grafting, coronary angiography revealing procedurally correctable stenosis managed conservatively and all-cause mortality.	6 weeks after inclusion
Subgroup analyses for diagnostic accuracy of the clinical decision rule	Subgroups are classified by; sex; region (Leiden, Maastricht, Venlo); socio-economic status (using postal-code); duration of symptoms (<2 hours, 2-6 hours, 6-12 hours, >12 hours, >24 hours) For the occurrence of ACS and MACE. MACE is defined as a combined endpoint of ACS, percutaneous coronary intervention, coronary artery bypass grafting, coronary angiography revealing procedurally correctable stenosis managed conservatively and all-cause mortality.	6 months after inclusion
Adherence to the recommendations of the clinical decision rule by general practitioners (GP)	Percentage of general practitioners following and deferring from the clinical decision rule, by comparing the GP's policy with the recommendations of the decision rule.	24 hours after inclusion
Diagnostic accuracy of the gut feeling/ presence of a sense of alarm from general practitioners	Diagnostic accuracy (i.e. sensitivity, negative predictive value) of general practitioner's gut feeling for Acute Coronary Syndrome and major adverse cardiac events (MACE). Using the Gut Feeling Questionnaire (GFC). The questionnaire consists of 11 items. The items use a 5-point Likert scale: completely disagree to completely agree. Items 1 and 11 are the same and ask the physician about their gut feeling: alarm vs reassuring. A high score indicates a sense of alarm (From Barais M, Fossard E, Dany A, et al. Accuracy of the general practitioner's sense of alarm when confronted with dyspnoea and/or chest pain: a prospective observational study. BMJ Open. 2020;10(2):e03434)	6 weeks after inclusion

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development; VieCuri Medical Centre; Maastricht Universitair Medisch Centrum
• Investigators: Principal Investigator: Tobias Bonten, MD PhD, LUMC

Publications and helpful links

General Publications

• van den Bulk S, Petrus AHJ, Willemsen RTA, Boogers MJ, Meeder JG, Rahel BM, van den Akker-van Marle ME, Numans ME, Dinant GJ, Bonten TN. Ruling out acute coronary syndrome in primary care with a clinical decision rule and a capillary, high-sensitive troponin I point of care test: study protocol of a diagnostic RCT in the Netherlands (POB HELP). BMJ Open. 2023 Jun 8;13(6):e071822. doi: 10.1136/bmjopen-2023-071822.

Helpful Links

• Up to date information about the study for patients and general practitioners (Dutch)
• Original registration on www.NTR.nl before start of the study

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2021
• Primary Completion (Actual): February 5, 2025
• Study Completion (Actual): April 23, 2025

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: April 11, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Primary care; Myocardial infarction; General practice; Chest pain; Troponin; Point of care test
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Ischemia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Myocardial Infarction; Acute Coronary Syndrome; Chest Pain
• Other Study ID Numbers: p20.013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the main article, after deidentification (text, tables, figures and appendices)
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following main article publication
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No