Early Vasopressors in Sepsis
ConditionSepsis
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorNHS Greater Glasgow and Clyde
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
>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
Trial design
Design model
Parallel
Treatments tested in this trial
Norepinephrine
DrugNorepinepherine should be prepared and delivered at a concentration of 16 micrograms/ml
Balanced Crystalloid
Other interventionIV fluids administered as per standard care
Treatment groups
1,006 Participants
are divided into 2 treatment groupsGroup A: Intervention ArmActive comparator 1 intervention
Group B: Standard carePlacebo comparator 1 intervention
Trial outcomes
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'.
Time frame
90 days post randomisationSecondary outcomes
1
Accumulated Total Volume of IV fluid
Accumulated volume of IV fluid delivered in each arm - excluding fluid volumes less than 100ml
Time frame
6,12, 24, 48 and 72 hours post randomisation2
Lactate clearance from baseline
Blood lactate value - arterial or venous
Time frame
6, 12, 24, 48 & 72 hours post randomisation3
Total Dose of Norepinephrine
Total dose of norepinephrine delivered by any route (peripheral or central) at each timepoint
Time frame
6, 12, 24, 48 and 72 hours post randomisation4
Proportion of patients who receive vasopressors
Proportion of patients recruited to control arm who receive any vasopressor (norepinephrine, vasopressin, metarminol, epinephrine) at each time point
Time frame
6, 12, 24 and 48 hours after recruitment to the control armOther outcomes
1
Patient Centred Outcome
organ support free days at 30 days
Time frame
30 days post randomisation2
Protocol Adherence
Proportion of patients who have PVI discontinued for non-clinical reasons after recruitment to intervention arm
Time frame
48 hours post randomisation3
Protocol Adherence
Proportion of patients in control arm who receive PVI
Time frame
48 hours post randomisation4
Organ Dysfunction Score
Organ dysfunction score (SOFA) calculated at Baseline
Time frame
Baseline Only (0 hours)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
NHS Greater Glasgow and Clyde
Lead sponsor
University of Edinburgh
Collaborator
Northern Care Alliance NHS Foundation Trust
Collaborator
University of Manchester
Collaborator
University of Glasgow
Collaborator
NHS Lothian
Collaborator
Chelsea and Westminster NHS Foundation Trust
Collaborator
Source ClinicalTrials.gov