Early Vasopressors in Sepsis
EVIS
2 other identifiers
interventional
1,006
1 country
25
Brief Summary
Sepsis is a life-threatening reaction to an infection. It happens when the immune system overreacts to an infection and starts to damage the body's tissues and organs. The aim of this research study is to compare the two different ways to treat sepsis, in the early phase of treatment immediately after the participants arrive in hospital. The standard approach is to give a salt solution fluid through a drip in the participants arm to start with, then adding in a medication that increases the blood flow to the participants vital organs (a vasopressor mediation called norepinephrine) if required. The alternative approach is to start the vasopressor medication immediately, and then add in extra salt solution fluid via a drip if required. Vasopressors work by increasing the blood pressure which allows a better blood flow to the internal organs. The investigators plan to see which approach is better and to see if they have a role in improving a patient's recovery time, reducing complications, the length of time they stay in hospital and longer term poor health. Based on research that has already been done, the investigators believe treating patients with vasopressors when they arrive in the Emergency Department, may have potential advantages over the standard fluids used today. However, the evidence is not clear and that is why this research is being done.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 sepsis
Started Oct 2022
Longer than P75 for phase_3 sepsis
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 11, 2021
CompletedFirst Posted
Study publicly available on registry
January 5, 2022
CompletedStudy Start
First participant enrolled
October 11, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2027
February 12, 2026
February 1, 2026
4.1 years
November 11, 2021
February 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The primary objective is to determine whether early PVI (within 12 hours of admission) targeted to MAP of ≥65 mmHg improves clinical effectiveness in hospitalised adult patients with septic shock compared with usual care, in the first 48 hours.
The primary objective is measured by the Primary outcome of 'Days Alive and Out of Hospital at 90 Days'.
90 days post randomisation
Secondary Outcomes (17)
Accumulated Total Volume of IV fluid
6,12, 24, 48 and 72 hours post randomisation
Lactate clearance from baseline
6, 12, 24, 48 & 72 hours post randomisation
Total Dose of Norepinephrine
6, 12, 24, 48 and 72 hours post randomisation
Proportion of patients who receive vasopressors
6, 12, 24 and 48 hours after recruitment to the control arm
Proportion of patients who require central venous access
24 and 48 hours post randomisation
- +12 more secondary outcomes
Other Outcomes (6)
Patient Centred Outcome
30 days post randomisation
Protocol Adherence
48 hours post randomisation
Protocol Adherence
48 hours post randomisation
- +3 more other outcomes
Study Arms (2)
Intervention Arm
ACTIVE COMPARATORParticipants will receive peripheral vasopressor infusion of norepinephrine (16 micrograms/ml) during the initial 48 hour study period. All other care will be as per local protocol.
Standard care
PLACEBO COMPARATORParticipants allocated to the control arm will receive standard care as defined by the UK NICE guidelines and the Surviving Sepsis Campaign guidelines during the 48 hour study period post randomisation. All other care will be as per local protocol.
Interventions
Norepinepherine should be prepared and delivered at a concentration of 16 micrograms/ml
Eligibility Criteria
You may qualify if:
- Age \>18 years
- Clinically suspected or proven infection resulting in principal reason for acute illness
- SBP \< 90 mmHg or MAP of \< 65 mmHg (within an hour of eligibility assessment)
- Measured serum lactate of \> 2 mmol/L. The serum lactate should be measured 2 hours prior to determination of eligibility, where possible. Longer timeframes may be used and justified within the medical notes if, in the opinion of the investigator, the clinical status of the patient has not significantly improved in the time interval between lactate measurement and eligibility assessment. Lactate measurements more than 4 hours prior to eligibility assessment should not normally be used.
- Hospital presentation within last 12 hours
You may not qualify if:
- \>1500ml of intravenous fluid prior to screening
- Clinically judged to require immediate surgery (within one hour of eligibility assessment)
- Immediate (\< 1 hour) requirement for central venous access
- Chronic renal replacement therapy
- Known allergy/adverse reaction to norepinephrine
- Palliation / end of life care (explicit decision by patient/family/carer in conjunction with clinical team that active treatment beyond symptomatic relief is not appropriate)
- Previous recruitment in the trial
- Patients with permanent incapacity
- Pregnancy. All women of childbearing potential (WoCBP) must have a negative urine or serum pregnancy test result completed as part of screening requirements.
- WoCBP are defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
- Other primary causes of shock (e.g. suspected cardiogenic shock, haemorrhagic shock, etc)
- History or evidence of any other medical, neurological or psychological condition that would expose the subject to an undue risk of a significant Adverse Effect as determined by the clinical judgement of the investigator
- Participation in other clinical trials of investigational medicinal products
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NHS Greater Glasgow and Clydelead
- University of Edinburghcollaborator
- Northern Care Alliance NHS Foundation Trustcollaborator
- University of Manchestercollaborator
- University of Glasgowcollaborator
- NHS Lothiancollaborator
- Chelsea and Westminster NHS Foundation Trustcollaborator
Study Sites (25)
Aintree University Hospital
Aintree, United Kingdom
Royal Blackburn Hospital
Blackburn, United Kingdom
Fairfield General Hospital
Bury, United Kingdom
Addenbrookes Hospital, Cambridge
Cambridge, United Kingdom
Royal Derby Hospital
Derby, United Kingdom
Royal Infirmary of Edinburgh
Edinburgh, United Kingdom
Victoria Hospital
Fife Keith, United Kingdom
Glasgow Royal Infirmary
Glasgow, United Kingdom
Queen Elizabeth University Hospital
Glasgow, United Kingdom
Hull Royal Infirmary
Hull, United Kingdom
Kettering General
Kettering, United Kingdom
University Hospital Crosshouse
Kilmarnock, United Kingdom
University Hospital Monklands
Lanark, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Royal Liverpool University Hospital
Liverpool, United Kingdom
Newham University Hospital
London, United Kingdom
Royal London Hospital
London, United Kingdom
St George's
London, United Kingdom
University Hospital Lewisham
London, United Kingdom
John Radcliffe Hospital
Oxford, United Kingdom
Royal Alexandra Hospital
Paisley, United Kingdom
Peterborough City Hospital
Peterborough, United Kingdom
Royal Berkshire Hospital
Reading, United Kingdom
Queens Hospital Barking
Romford, United Kingdom
Salford Royal
Salford, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 11, 2021
First Posted
January 5, 2022
Study Start
October 11, 2022
Primary Completion (Estimated)
November 1, 2026
Study Completion (Estimated)
October 1, 2027
Last Updated
February 12, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share
to be confirmed