Prehospital Triage of Patients With Severe Shortness of Breath Using Biomarkers

Study Overview
=================
Brief Summary
-----------------
Breathlessness is a dangerous symptom. Preliminary data from national and regional Danish databases show, that patients with shortness of breath in the ambulance have a very high mortality. Breathlessness can be caused by many different conditions - but heart diseases and lung diseases are dominant. The mortality is especially high in patients with breathlessness caused by heart disease. Distinguishing these different causes of breathlessness is a classical, often difficult, discipline in medicine. Visitation and guidance of treatment in patients with breathlessness in the prehospital setting relies on medical history and physical examination and as a consequence prehospital treatment for breathlessness is often non-specific. The use of heart-failure specific biomarkers may improve prehospital visitation and treatment of patients with breathlessness. We hypothesize, that Supplementing the routine examination by prehospital anesthesiologist with measurement of a biomarker for heart failure increases the proportion of patients with severe shortness of breath caused by heart disease triaged directly to department of cardiology This strategy does not increase the proportion of patients with severe shortness of breath caused by non-heart disease triaged directly to department of cardiology

Detailed Description
-----------------
Measurement of the biomarker for heart failure N-terminal pro-Brain Natriuretic Peptide (NT-proBNP): In patients randomized to the strategy with supplementary measurement of NT-proBNP, a blood sample will be drawn from the peripheral venous catheter that is routinely inserted. This will be analyzed point-of-care in the ambulance. Interpretation of NT-proBNP: Cut-off values based on bootstrap-validated optimal cut-points for heart failure on will be used. Confirmatory ('rule in') cut point < 50 years: 450 pg/mL 50-75 years: 900 pg/mL > 75 years: 1800 pg/mL Exclusionary ('rule out') cut point All patients: 300 pg/mL The emergency physicians will be thoroughly informed about these cut-points, but told not to triage to department of cardiology or other department strictly according to NT-proBNP, but according to clinical assessment AND NT-proBNP.

Official Title
-----------------
Prehospital Triage of Patients With Severe Dyspnea Using Point-of-Care N-terminal Pro-Brain Natriuretic Peptide. PreBNP Trial.

Conditions
-----------------
Dyspnea

Intervention / Treatment
-----------------
* Other: Supplementary NT-proBNP measurement


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients requiring dispatch of emergency physician because of severe dyspnea. Severe dyspnea is defined by dyspnea plus at least ONE of the following Respiration frequency > 20 or < 8 Saturation < 96 without supplementary oxygen Heart rate > 100 or < 50 Systolic blood pressure < 100 or > 200 Difficulty talking Central or peripheral cyanosis Use of accessory muscles of respiration Glasgow coma scale score < 15 AND because of the physical condition, the patient is not able to give informed consent Exclusion Criteria Age < 18

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Business as usual<br>Triage and treatment based on routine clinical assessment as usual | |
| Experimental: Supplementary NT-proBNP measurement<br>Triage and treatment based on routine clinical assessment supplemented with measurement of NT-proBNP | Other: Supplementary NT-proBNP measurement<br>* In patients randomized to the strategy with supplementary measurement of NT-proBNP, a blood sample will be drawn from the peripheral venous catheter that is routinely inserted and analyzed immediately using a COBAS H232 and Roche Diagnostics NT-proBNP assay.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with dyspnea caused by heart disease initially triaged to department of cardiology | An endpoint committee determines final diagnoses as dyspnea caused by heart disease, dyspnea caused by lung disease and dyspnea caused by other diseases based on clinical and paraclinical data excluding prehospital NT-pro-BNP value | Within 1 day from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with dyspnea of other etiologies initially triaged to department of cardiology | An endpoint committee determines final diagnoses as dyspnea of cardiac origin and dyspnea of non-cardiac origin based on clinical and paraclinical data excluding prehospital NT-pro-BNP value | Within 1 day from randomization | 
| Proportion of patients with dyspnea caused by heart disease that receives pulmonary medication | beta2-agonist inhalations, combined ipratropium/b2-agonist inhalations, intravenous b2-agonists, intravenous corticosteroids | Within 1 day | 
| Length of hospital stay | Time from hospital admission related to the inclusion event to discharge from hospital | Up to three months from randomization | 
| Intensive care unit admission rate | Within the time from hospital admission related to the inclusion event to discharge from hospital related to inclusion event | Up to three months from randomization | 
| All-cause re-admission |  | Within 3 months of randomization | 
| Proportion of patients not admitted to hospital | Proportion of patients not admitted to hospital in relation to the inclusion event | Within 24 hours | 
| All-cause mortality |  | Within 30 days of randomization | 
| Proportion of patients with dyspnea caused by lung disease, that receives traditional heart failure medication | Loop diuretics, nitrates, opiates | Within 1 day | 
| Proportion of patients with correct diagnosis of congestive heart failure in the prehospital setting | An endpoint committee determines final diagnoses based on clinical and paraclinical data excluding prehospital NT-pro-BNP value | Within 1 day of randomization | 
| Proportion of patients where congestive heart failure is correctly disproved in the prehospital setting | An endpoint committee determines final diagnoses based on clinical and paraclinical data excluding prehospital NT-pro-BNP value | Within 1 day of randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dyspnea, Prehospital, Biomarker, Heart failure, Triage, Randomized, controlled study