Early Initiated Vasopressor Therapy in the Emergency Department

Study Overview
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Brief Summary
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The goal of this pragmatic, multi-center, superiority, randomized clinical trial is to compare early treatment with peripheral (through a vein) infused noradrenaline (a natural hormone that increases blood pressure) with fluid only therapy in patients with hypotensive and shock in the Danish Emergency Departments (ED). The main questions it aims to answer are: If early initiated noradrenaline in non-bleeding hypotensive patients presenting in the ED can Improve time to shock control. Reduce the need for ICU admittance. Decrease mortality. Participants will be included by the clinical staff and treated urgently with either noradrenaline or usual treatment during their Emergency Department stay. After completion of the treatment in the Emergency Department, patient data will be extracted from the bed-side measurements, electronic health records and national registers. Patients will be contacted by the research staff 1 year after study inclusion to answer brief questions about their daily physical function and ability to care for themselves. Researchers will compare with patients receiving fluid therapy only, as this is the usual standard of care in Danish Emergency Departments.

Detailed Description
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Please refer to the full protocol.

Official Title
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Early Initiated Vasopressor Therapy vs. Standard Care of Primarily Fluid Therapy in Hypotensive Patients in the Emergency Department - A Pragmatic, Multi-center, Superiority, Randomized Controlled Trial

Conditions
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Hypovolemic Shock, Hypovolemic, Shock, Shock, Septic, Hypotension, Hypotension and Shock, Hypotension Symptomatic, Hypovolemia

Intervention / Treatment
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* Drug: Noradrenaline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age Signs or suspicion of hypotension or shock (Defined as SBP < 100mmHg or MAP < 65 mmHg combined with lactate > 2.0 mmol/L or by physician defined blood pressure for the individual patient combined with a lactate > 2.0 mmol/L). Received at least 500ml of intravenous fluid before study inclusion (Including prehospital administration) within the first 4 hours of ED arrival. Clinical Frailty Score (CFS), see appendix 2, of ≤4. If CFS is ≥5 and the treating physician find the patient suitable for ICU admittance, the participant can be enrolled, if the on-call ICU doctor would accept the patient for ICU admittance. If the treating physician is unsure of ICU eligibility, regardless of CFS score, the patient should be consulted with the ICU consultant before study inclusion. Exclusion Criteria: Cardiogenic, anaphylactic, haemorrhagic, or neurogenic shock suspected by the treating physician. Fertile women (<60 years of age) with positive urine human gonadotropin (hCG) or plasma-hCG or women breastfeeding. Patient deemed terminally ill or with a severe co-morbid status resulting in non-eligibility for ICU admittance decided by either the treating physician or ICU consultant. Known allergy to noradrenaline.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Peripheral noradrenaline will be infused at rates of 0.05-0.15 mcg/kg/min for up to 24 hours after randomization in the ED until shock control is achieved. If shock control cannot be achieved, patients will be transferred to the ICU for further treatment of their condition but without further trial intervention. Weaning of intervention will be completed during the 24 hours, and if possible, terminated. If termination of treatment is not achievable within 24 hours, participants will be transferred to the ICU. | Drug: Noradrenaline<br>* See arm description<br>* Other names: ATC-code C01CA03;|
| No Intervention: Control<br>No ED administered noradrenaline. Standard care of hypotension and shock in the Danish ED's are fluid therapy and if not possible to achieve shock control, they are transferred to the ICU for administration of vasopressors if they are eligible for ICU admittance. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving either systolic blood pressure (SBP) >100 mmHg or mean arterial pressure (MAP) > 65 mmHg or a target blood pressure set by the treating physician at 90 minutes after inclusion | Bed-side assessment during treatment and registered in the case report form. | At 90 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of intensive care unit (ICU) free days alive within 30 days | Data is extracted from the Danish national registries or the patient's electronic medical record. | At 30 days | 
| Hours without shock within 24 hours | Bed-side assessment during treatment and registered in the case report form or by extraction from the patient's electronic medical record. | At 24 hours | 
| 30-day all-cause mortality | Data is extracted from the Danish national registries or the patient's electronic medical records. | At 30 days | 
| In-hospital mortality | Data is extracted from the Danish national registries or the patient's electronic medical records. | At hospital discharge, an average of 30 days efter inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluid therapy, Peripherally infused noradrenaline, Fluid treatment, Non-hemorrhagic shock and hypotension, Emergency Department