Akershus Cardiac Examination 4 Study

Study Overview
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Brief Summary
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Patients hospitalized with tachypnea, defined as respiratory rate ≥20/ min, have substantial mortality and may suffer from different conditions, including acute heart failure (HF). Symptoms of HF can be difficult to identify and  15% of patients with HF will not be correctly diagnosed by the treating physician in the Emergency Department. Biomarkers like B-type natriuretic peptides and cardiac troponins improve diagnostic accuracy and risk stratification. Whether early, structured biomarker assessment and structured feedback in the patient's electronic health records improve management and outcomes among unselected patients with tachypnea have previously not been explored in a randomized controlled trial. The main research question of the study is to determine whether early structured biomarker assessment in unselected patients with tachypnea extends the time to the first event for either (1) all-cause readmission or (2) all-cause mortality; i.e. time to the combined endpoint, compared to the current strategy/standard care

Official Title
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Akershus Cardiac Examination (ACE) 4 Study: Pragmatic Randomized Controlled Trial of Early Biomarker Measurements and Structured Feedback in Unselected Patients With Tachypnea

Conditions
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Heart Failure, Tachypnea

Intervention / Treatment
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* Other: Early biomarker-based cardiological assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years old Tachypnea (respiratory rate ≥20/min) Admission to Departments under the Division of Medicine at Akershus University Hospital, except the Department of Neurology <24 h from hospital admittance to inclusion in the study Signed written informed consent during the initial phase of the hospitalization Exclusion Criteria: Previously included into the study (in case of patients presenting with a second hospitalization during the study period) Known or suspected cancer outside of local control, documented in medical records, at the time of patient inclusion or diagnosed in relation to the index hospitalization Neurological condition with short life expectancy; e.g. ALS, documented in medical records during screening prior to study entry Other non-cardiac disease with life expectancy below 1 year, documented in medical records during screening prior to study entry Obvious non-cardiac cause for tachypnea based on medical records and clinical findings during screening prior to study entry; e.g. anaphylaxis in young patient with known allergy, dyspnea after direct chest trauma, or young patient with fever and positive Covid-19 test on admission. Patient assessed as non-Internal Medicine patient; e.g. surgical patient Patients unwilling or unable to comply with the protocol, including Glasgow Coma Scale <13 on the time of study inclusion Patients that are intubated for invasive ventilatory therapy before or shortly after hospital admission History of non-compliance to medical management and patients who are considered potentially unreliable, based on documentation in medical records, during screening prior to study entry History or evidence of alcohol or drug abuse with the last 12 months, based on medical records and clinical findings during screening prior to study entry, that will influence study participation Any surgical or medical condition, based on medical records and clinical findings during screening prior to study entry, that will impair the ability of the patient to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early biomarker-based cardiological assessment and structured feedback in the EHR<br>We will perform cardiac biomarker testing with NT-proBNP and hs-cTnT measurements on emergency department admission in all participants, regardless of randomization status. The results will be provided in the patient's EHR, regardless of randomization status. For patients randomized to the intervention group, we will provide a note in the patient's EHR that includes assessment of probability that myocardial injury or dysfunction are the underlying pathophysiology responsible for tachypnea, as evaluated by the cardiac biomarker algorithm of the study. We will inform on general recommendations for work up and treatment. | Other: Early biomarker-based cardiological assessment<br>* We will perform cardiac biomarker testing with NT-proBNP and hs-cTnT measurements on emergency department admission in all participants, regardless of randomization status. The results will be provided in the patient's EHR, regardless of randomization status. For patients randomized to the intervention group, we will provide a note in the patient's EHR that includes assessment of probability that myocardial injury or dysfunction are the underlying pathophysiology responsible for tachypnea, as evaluated by the cardiac biomarker algorithm of the study. We will inform on general recommendations for work up and treatment.<br>|
| No Intervention: Standard of care<br>Routine standard of care according to the treating physician | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of all-cause hospital readmission or all-cause mortality | Composite of all-cause hospital readmission or all-cause mortality after discharge from index hospitalization | 12 months after discharge from index hospitalization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital length of stay | Hospital length of stay during the index hospitalization | From admission to discharge of index hospitalization, assessed up to 12 months | 
| Length of stay in Intensive Care Unit/Medical Intensive Care Unit/Cardiac Intensive Care Unit | Length of stay in Intensive Care Unit/Medical Intensive Care Unit/Cardiac Intensive Care Unit during the index hospitalization | From admission to discharge of index hospitalization, assessed up to 12 months | 
| 30-day all-cause readmission | 30-day all-cause readmission after discharge from index hospitalization | 30-days after discharge from index hospitalization | 
| Time to all-cause readmission | Time to first all-cause readmission after discharge from index hospitalization | 12 months after discharge from index hospitalization | 
| Number of all-cause readmission | Number of all-cause readmissions after discharge from index hospitalization | 12 months after discharge from index hospitalization | 
| All-cause mortality | Time to all-cause mortality after discharge from index hospitalization | 12 months after discharge from index hospitalization | 
| Total cost of hospitalization | Total cost of hospitalization | From admission to discharge of index hospitalization, assessed up to 12 months | 
| All-cause mortality | All-cause mortality during the index hospitalization | From admission to discharge of index hospitalization, assessed up to 12 months | 
| Difference in cardiac biomarker concentrations during index hospitalization | Difference in the cardiac troponin T and/or I and B-type natriuretic peptide and/or N-terminal pro-B-type natriuretic peptide concentrations from hospital admission to discharge | From admission to discharge of index hospitalization, assessed up to 12 months | 
| Difference in guideline-defined medical therapy for heart failure | Difference in guideline-defined medical therapy for heart failure, as defined by international guidelines, at discharge after index hospitalization | From admission to discharge of index hospitalization, assessed up to 12 months | 
| Cost-utility | Cost-utility for the intervention strategy | From admission to discharge of index hospitalization, assessed up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biomarker, tachypnea, heart failure, echocardiography