Early Initiated Vasopressor Therapy in the Emergency Department (VASOSHOCK)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Shock; Shock, Septic; Hypotension; Hypovolemia; Hypotension and Shock; Hypovolemic Shock; Hypotension Symptomatic; Hypovolemic
• Intervention / Treatment: Drug: Noradrenaline

Detailed Description

Please refer to the full protocol.

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lasse P Bentsen, MD; Phone Number: +4520496950; Email: lasse.paludan.bentsen@rsyd.dk

Study Locations

• Denmark
  • Esbjerg, Denmark, 6700
    • Not yet recruiting
    • Esbjerg Hospital
    • Contact: Peter Biesenbach, MD
    • Principal Investigator: Peter Biesenbach, MD
  • Herning, Denmark, 7400
    • Not yet recruiting
    • Gødstrup Regional Hospital
    • Contact: Larshan Perinpam, MD
    • Principal Investigator: Larshan Perinpam, MD
  • Køge, Denmark, 4600
    • Not yet recruiting
    • Zealand University Hospital
    • Contact: Gerhard Tiwald, MD, DMSc
    • Principal Investigator: Gerhard Tiwald, MD, DMSc
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Lasse P Bentsen, MD
    • Principal Investigator: Lasse P Bentsen, MD
    • Sub-Investigator: Mikkel Brabrand, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; 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; See arm description; Other Names: ATC-code C01CA03
No Intervention: Control; 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?

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

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Investigators: Principal Investigator: Lasse P Bentsen, MD, Department of Emergency Medicine, Odense University Hospital; Study Chair: Mikkel Brabrand, MD, PhD, Department of Emergency Medicine, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: June 19, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): July 5, 2023

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Emergency Department; Fluid therapy; Fluid treatment; Peripherally infused noradrenaline; Non-hemorrhagic shock and hypotension
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Emergencies; Shock, Septic; Shock; Hypotension; Hypovolemia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: OP_1749

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No