Clinical trial NCT05931601: Early Initiated Vasopressor Therapy in the Emergency Department
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Shock
Shock, Septic
Hypotension
Hypotension and Shock
Hypotension Symptomatic
Hypovolemia
Hypovolemic Shock
Hypovolemic
Keywords: Peripherally infused noradrenaline
Fluid therapy
Fluid treatment
Non-hemorrhagic shock and hypotension
Emergency Department
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2023-07-05
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: Please refer to the full protocol.

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age
* Signs or suspicion of hypotension or shock (of any type such as septic, vasodilatory or hypovolemic not included in the exclusion criteria) defined as:

  1. SBP \< 100mmHg or MAP \< 65 mmHg combined with lactate \> 2.0 mmol/L,
  2. Physician defined blood pressure for the individual patient combined with a lactate \> 2.0 mmol/L
  3. Either SBP \< 100mmHg or MAP \< 65mmHg with obvious signs of shock with any lactate level evaluated by either two non-specialist physicians (e.g. registrar medical doctors) or a specialist physician.
* 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) 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.

Primary outcomes:
measure: The primary outcome is the proportion of patients achieving either SBP >100 mmHg or MAP > 65 mmHg or a target blood pressure set by the treating physician at 90 (±15) minutes after inclusion.
timeFrame: At 90 minutes
Secondary outcomes:
measure: Number of intensive care unit (ICU) free days alive within 30 days
timeFrame: At 30 days
measure: Time without shock within 24 hours
timeFrame: At 24 hours
measure: 30-day all-cause mortality
timeFrame: At 30 days
measure: In-hospital all-cause mortality
timeFrame: At hospital discharge, an average of 30 days efter inclusion
Other outcomes:
measure: Proportion of patients receiving vasopressor at any point within 24 hours
timeFrame: At 24 hours
measure: Time to vasopressor initiation
timeFrame: At 30 days
measure: Hours of vasopressor infusion
timeFrame: At 30 days
measure: Proportion of patients with pulmonary oedema within 72 hours
timeFrame: At 72 hours
measure: Proportion of patients with acute kidney failure within 72 hours
timeFrame: At 72 hours
measure: Number of organ support free days alive within 30 days
timeFrame: At 30 days
measure: Number of organ support free days alive within 30 days
timeFrame: At 30 days
measure: Proportion of patients admitted to the ICU
timeFrame: At 30 days
measure: ED Length of stay
timeFrame: At 72 hours
measure: ICU length of stay
timeFrame: At 30 days
measure: Hospital length of stay
timeFrame: At 30 days
measure: Proportion and duration of mechanical ventilation
timeFrame: At 30 days
measure: Proportion and length of renal replacement therapy
timeFrame: At 30 days
measure: Amount of fluid therapy within the first 24 hours
timeFrame: At 24 hours
measure: Proportion of serious adverse events for noradrenaline or fluid therapy, e.g. extravasation or overdosis of noradrenaline, pulmonary edema, new cardiac arrhytmias, during the intervention of control period
timeFrame: At 24 hours
Locations:
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Esbjerg
country: Denmark
facility: Esbjerg Hospital
city: Herning
country: Denmark
facility: Gødstrup Regional Hospital
city: Køge
country: Denmark
facility: Zealand University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Department of Emergency Medicine, Odense University Hospital
name: Lasse P Bentsen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Emergency Medicine, Odense University Hospital
name: Mikkel Brabrand, MD, PhD
role: STUDY_CHAIR
References: