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

Study Overview
=================
Brief Summary
-----------------
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: 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. What is the accuracy (sensitivity, negative prediction value) of the clinical decision rule for excluding ACS and MACE at 6 weeks and 6 months?

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.

Official Title
-----------------
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

Conditions
-----------------
Chest Pain, Myocardial Infarction, Acute Coronary Syndrome

Intervention / Treatment
-----------------
* Diagnostic Test: Clinical decision rule


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A clustered randomized controlled trial in which general practices are randomized to the intervention- or control group in 2:1 ratio.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clinical decision rule<br>Patients in whom the clinical decision rule is used to exclude acute coronary syndrome | Diagnostic Test: Clinical decision rule<br>* 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<br>|
| No Intervention: Standard care<br>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 | 
| 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 | 
| 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 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chest pain, Primary care, General practice, Myocardial infarction, Troponin, Point of care test