Here is the design of a clinical trial:

Official Title: A Multicentre Randomized Controlled Trial to Improve the accUracy of Referrals to the emerGency departmEnt of patieNts With chesT Pain by Using the Modified HEART Score in Emergency Medical Transport (URGENT 2.0)

Included conditions:
- Chest Pain
- Acute Coronary Syndrome
- Myocardial Infarction
- Myocardial Ischemia
- Heart Attack

Study Armgroups:
- {'label': 'Intervention group', 'type': 'EXPERIMENTAL', 'description': 'Chest pain patients in the intervention group will be assessed by EMT personnel by performing the modified HEART score (including POC high sensitive troponin-I measurement (POC HS cTnI)) and the referral policy depends on the result.\n\n* In case of a low modified HEART score (modified HEART 0-3) patients will not be referred to the cardiac ED.\n* Patients with a modified HEART score \\>3 are directly referred to the cardiac ED after evaluation. These patients will receive standard care.', 'interventionNames': ['Diagnostic Test: modified HEART score (including POC hs cTnI analysis)']}
- {'label': 'Control group', 'type': 'ACTIVE_COMPARATOR', 'description': 'Chest pain patients in the control group will receive standard triage and standard care according to the local (EMT) protocol.', 'interventionNames': ['Other: Standard care and triage according to the local (EMT)protocol.']}

Interventions:
- {'type': 'DIAGNOSTIC_TEST', 'name': 'modified HEART score (including POC hs cTnI analysis)', 'description': 'The modified HEART score was developed in 2007 and has been validated to stratify the risk of short-term adverse cardiac events in patients with chest pain at the ED. Negative predictive value (NPV) of the modified HEART score for ACS as well as positive predictive value (PPV) for major adverse cardiac events (MACE) within 6 weeks after presentation is high.\n\nThe modified HEART score is an acronym for history, ECG, age, risk factors and troponin at arrival.The components can be rated 0,1 or 2 points each and result in a total score between 0 and 10.', 'armGroupLabels': ['Intervention group']}
- {'type': 'OTHER', 'name': 'Standard care and triage according to the local (EMT)protocol.', 'description': 'Standard care and triage of chest pain patients according to the local (EMT)protocol.', 'armGroupLabels': ['Control group']}

Primary Outcomes:
- {'measure': 'The incidence of non-cardiac chest pain (NCCP) patients admitted at the cardiac ED (percentage, %)', 'description': 'Evaluation of the percentage of NCCP patients admitted to the cardiac ED by performing the modified HEART score in comparison to our control group (regular triage and care). We aim to detect a reduction of minimal 10% in unnecessarily referred chest pain patients (NCCP patients) but expect an even higher percentage. A lower percentage of NCCP patients indicates improval of the triage of chest pain patients.', 'timeFrame': '30 days'}
- {'measure': 'The incidence of MACE (percentage, %)', 'description': 'The mortality and major adverse cardiovascular events (MACE) i.e. acute myocardial infarction, non-elective percutaneous coronary intervention, coronary artery bypass grafting or all cause death within 30 days, 6 months and 1 year after initial presentation in the intervention group versus control group.\n\nWe aim that the proportion of MACE in the intervention group (modified HEART score) is non-inferior to the control group (regular care and triage). Preliminary results of the second phase of FAMOUS Triage trial showed 15.7% (13.1-18.6) MACE rate.We used the expected incidence of 15.7% as the point estimate (meaning no difference between control and intervention). A higher MACE rate (%) in the intervention group suggests a worst outcome.', 'timeFrame': '30 days, 6 months and 1 year'}

Please estimate the sample size based on the assumption: 
A power of 80% and a two-tailed type I error of 5% for the primary endpoint; 90% power and a one-sided 95% CI (or equivalently a 90% two-sided CI) for the safety endpoint. Correction for loss to follow-up is also considered.
Sample size calculation
        A large sample size is required to adequately power both the efficacy and safety endpoint and for the eventual implementation of the modified HEART score in the prehospital setting.
        A baseline registry performed at our hospital in 2015 showed that 74.5% of the patients who contacted the GPC were unnecessarily referred to the ED with suspected ACS.22 For the sample size calculation based on the primary endpoint, we used the clinical calculator (https://clincalc.com/stats/samplesize.aspx). Aiming at a power of 80% and a two-tailed type I error of 5%, 328 patients need to be enrolled within this study in each study group (the intervention and control group) in order to be able to demonstrate a reduction of 10% in unnecessarily referred patients.
        The sample size calculation for the safety endpoint is based on demonstrating that the proportion of MACE in the intervention group is non-inferior to that in the control group. Preliminary results of the second phase of the FAMOUS Triage trial showed a 15.7% (13.1â18.6) MACE rate.23 We used the expected incidence of 15.7% as the point estimate (meaning no difference between the control group and the intervention group). Phase 3 of the FAMOUS Triage trial is a non-inferiority trial, controlled beforeâafter multicentre study with a sequential design with the aim to assess feasibility and safety of prehospital risk assessment by paramedics using the HEART score.24 Based on the study design paper of this trial, we set the non-inferiority margin at 7.5%. For the sample size calculation, we used the clinical calculator (see https://www.sealedenvelope.com/power/binary-noninferior/).
        If there is truly no difference between the standard and experimental treatment (15.7% in both groups), then 808 patients are required to be 90% sure that the upper limit of a one-sided 95% CI (or equivalently a 90% two-sided CI) will exclude a difference in favour of the standard group of more than 7.5%.
        To correct for loss to follow-up, we will include 426 patients in the intervention group and 426 patients in the control group, adding up to a total study population of 852 patients.